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Cited by 12IL-33, ST2, and ILC PathwaysChronic Obstructive Pulmonary Disease (COPD) ResearchAsthma and respiratory diseases

Picroside II Isolated from Pseudolysimachion rotundum var. subintegrum Inhibits Glucocorticoid Refractory Serum Amyloid A (SAA) Expression and SAA-induced IL-33 Secretion

Open access
Lee, Kiram, Choi, Jin, Choi, Bo Kyong, Gu, Young-Mi, Ryu, Hyung Won, Oh, Sei-Ryang, Lee, Hyun-Jun·2019·Molecules
DOI 10.3390/molecules24102020PMC PMC6572537
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Abstract

Chronic obstructive pulmonary disease (COPD) is a major inflammatory lung disease characterized by irreversible and progressive airflow obstruction. Although corticosteroids are often used to reduce inflammation, steroid therapies are insufficient in patients with refractory COPD. Both serum amyloid A (SAA) and IL-33 have been implicated in the pathology of steroid-resistant lung inflammation. Picroside II isolated from Pseudolysimachion rotundum var. subintegrum (Plantaginaceae) is a major bioactive component of YPL-001, which has completed phase-2a clinical trials in chronic obstructive pulmonary disease patients. In this study, we investigated whether picroside II is effective in treating steroid refractory lung inflammation via the inhibition of the SAA-IL-33 axis. Picroside II inhibited LPS-induced SAA1 expression in human monocytes, which are resistant to steroids. SAA induced the secretion of IL-33 without involving cell necrosis. Picroside II, but not dexamethasone effectively inhibited SAA-induced IL-33 expression and secretion. The inhibitory effect by picroside II was mediated by suppressing the mitogen-activated protein kinase (MAPK) p38, ERK1/2, and nuclear factor-κB pathways. Our results suggest that picroside II negatively modulates the SAA-IL-33 axis that has been implicated in steroid-resistant lung inflammation. These findings provide valuable information for the development of picroside II as an alternative therapeutic agent against steroid refractory lung inflammation in COPD.

AI snapshot

Written from the paper’s full text.

TL;DR

Picroside II, a bioactive component of YPL-001, inhibits LPS-induced SAA1 expression in human monocytes and SAA-induced IL-33 expression/secretion in human airway epithelial cells. Its effects are mediated through TLR2 and suppression of p38, ERK1/2, and NF-κB signaling, suggesting potential against glucocorticoid-refractory lung inflammation in COPD.

Key findings

  • Picroside II dose-dependently suppressed LPS-induced SAA1 mRNA in THP-1 human monocytes, whereas dexamethasone (DEX) enhanced LPS-induced SAA1 mRNA; picroside II also reduced SAA1 mRNA induced by LPS plus DEX. Picroside II did not inhibit LPS-induced TNFα expression, while DEX did.
  • Recombinant human SAA dose-dependently upregulated IL33 gene expression and induced IL-33 secretion in NCI-H292 airway epithelial cells, with secretion detected at 0.1 μg/mL and maximal at 0.2 μg/mL; IL-33 release increased after 2 h, further increased to 6 h, and returned to normal by 12 h. SAA-induced IL-33 was not due to LPS contamination or necrosis, as polymyxin B did not affect it and LDH activity was undetectable.
  • SAA-induced IL-33 secretion was significantly blocked by SB203580 (p38 inhibitor), PD98059 (ERK1/2/MEK-1 inhibitor), and Bay11-7082 (IKKβ inhibitor), but not by LY294002 (PI3K inhibitor). Neutralizing antibodies against TLR2 and TLR4 blocked SAA-induced IL-33 secretion and reduced ERK1/2 and IκBα phosphorylation, and completely blocked p38 phosphorylation.
  • Picroside II dose-dependently reduced SAA-induced IL33 mRNA and IL-33 protein secretion; DEX did not affect SAA-induced IL33 mRNA. Both picroside II and DEX inhibited Pam3CSK4-mediated IL-33 expression/secretion. Picroside II reduced SAA-induced phosphorylation of p38, ERK1/2, IκBα, and p65, whereas DEX did not.

Methods

  • Human cell lines: THP-1 monocytes and NCI-H292 airway epithelial cells, stimulated with LPS, DEX, recombinant human SAA, Pam3CSK4, signaling inhibitors, or neutralizing antibodies against TLR2/TLR4.
  • Main assays: RT-qPCR for SAA1, IL33, TNF, and reference genes; ELISA for IL-33 secretion; Western blot for phospho-p38, phospho-ERK1/2, phospho-IκBα, and phospho-p65; LDH and Hoechst/PI staining for cytotoxicity.
  • Statistics: results expressed as means ± SEMs of three independent experiments; ANOVA followed by multiple comparison with Dunnett’s adjustment; significance at P < 0.05.

Limitations

  • Stated in the paper: further studies are needed to verify whether picroside II inhibits SAA protein secretion, to test effects on macrophages derived from COPD patients, and to determine picroside II’s exact molecular target in SAA signaling.
  • Stated in the paper: the precise mechanism of SAA and IL-33 inhibition by picroside II requires further study.
  • Evident from the text: all experiments used cell lines rather than primary COPD patient cells or in vivo COPD models, and no clinical outcomes or SAA protein measurements in monocytes are reported.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/molecules24102020

Cites

36 of 36 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

22 of 33 cited sources checked · 16 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Verproside is predominantly metabolized to picroside II in vivo.

    “Verproside is predominantly metabolized to picroside II in vivo [18].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [18] Kim, 2012, In vitro and in vivo metabolism of verproside in rats, Molecules source

      The Results and Discussion identify picroside II as a verproside metabolite and report more of it than isovanilloylcatalpol in rat bile and urine. The Conclusions describe O-methylation to both compounds, followed by glucuronidation and sulfation, as the major pathway in rats; they do not establish picroside II alone as the predominant product in vivo generally. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
  • Premisecitation

    IL-33 is implicated as a steroid-resistant mediator that promotes airway remodeling in patients with severe therapy-resistant asthma.

    “Moreover, IL-33 has been implicated as a steroid-resistant mediator that promotes airway remodeling in patients with severe therapy-resistant asthma [15].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [15] Saglani, 2013, IL-33 promotes airway remodeling in pediatric patients with severe steroid-resistant asthma, J. Allergy Clin. Immunol. source
  • Premisecitation

    Picroside II has therapeutic potential for allergic asthma in HDM-induced asthmatic mice.

    “Recently, we demonstrated that picroside II has therapeutic potential for allergic asthma in HDM-induced asthmatic mice [19].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [19] Choi, J., Choi, B.K., Kim, J.S., Lee, J.W., Park, H.A., Ryu, H.W., Lee, S.U., Hwang, K.W., Yun, W.K., and Kim, H.C. (2016). Picroside II Attenuates Airway Inflammation by Downregulating the Transcription Factor GATA3 and Th2-Related Cytokines in a Mouse Model of HDM-Induced Allergic Asthma. PLoS ONE, 11. source
  • Premisecitation

    Increase in serum level of SAA is associated with glucocorticoid resistance.

    “A recent article reported that the increase in the serum level of serum amyloid A (SAA) is associated with glucocorticoid resistance [6].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [6] Bozinovski, 2012, Serum amyloid A opposes lipoxin A(4) to mediate glucocorticoid refractory lung inflammation in chronic obstructive pulmonary disease, Proc. Natl. Acad. Sci. USA source

      The Abstract (page not provided) reports increased circulating SAA during COPD exacerbations and identifies SAA as a candidate mediator of glucocorticoid-refractory lung inflammation. It does not establish that higher serum SAA levels themselves are associated with measured glucocorticoid resistance; the resistance findings concern lung inflammation and local SAA production. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Premisecitation

    SAA/IL-33 play a role in the pathology of steroid-resistant lung inflammation.

    “It has been shown that SAA/IL-33 play a role in the pathology of steroid-resistant lung inflammation [6,15].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [6] Bozinovski, 2012, Serum amyloid A opposes lipoxin A(4) to mediate glucocorticoid refractory lung inflammation in chronic obstructive pulmonary disease, Proc. Natl. Acad. Sci. USA source
    • cites [15] Saglani, 2013, IL-33 promotes airway remodeling in pediatric patients with severe steroid-resistant asthma, J. Allergy Clin. Immunol. source
  • Classified as probably not a substantial claim. 13
  • May combine two claims. 13

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    NF-κB regulates expression of various inflammatory cytokines including TNF-α.

    “NF-κB regulates expression of various inflammatory cytokines including TNF-α [34].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [34] Edwards, 2009, Targeting the NF-kappaB pathway in asthma and chronic obstructive pulmonary disease, Pharmacol. Ther. source

  • Classified as probably not a substantial claim.

    Premisecitation

    IL-33 is released during necrotic cell death.

    “IL-33 is also released during necrotic cell death [21].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [21] Lamkanfi, 2009, IL-33 raises alarm, Immunity source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Elevated IL-33 concentrations in nuclei of airway epithelial cells are observed in patients with COPD.

    “Elevated IL-33 concentrations in the nuclei of airway epithelial cells are observed in patients with COPD [14].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [14] Byers, 2013, Long-term IL-33-producing epithelial progenitor cells in chronic obstructive lung disease, J. Clin. Investig. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    SAA stimulates release of cytokines including IL-23, IL-1β, TNF-α, and IL-8 in specific cell types.

    “SAA has been known to stimulate the release of cytokines including IL-23, IL-1β, TNF-α, and IL-8 in specific cell types [11,12,13].”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [11] He, 2006, Serum amyloid A is an endogenous ligand that differentially induces IL-12 and IL-23, J. Immunol. source
    • cites [12] Migita, K., Izumi, Y., Jiuchi, Y., Kozuru, H., Kawahara, C., Nakamura, M., Nakamura, T., Agematsu, K., Masumoto, J., and Yasunami, M. (2014). Serum amyloid A induces NLRP-3-mediated IL-1beta secretion in neutrophils. PLoS ONE, 9. source

      The Results section reports that SAA stimulated secretion of mature IL-1β from human neutrophils. The paper's References list studies concerning SAA-induced TNF-α and IL-8 release, but the paper does not report an IL-23 finding. Thus, this source supports part, but not all, of the cytokine list attributed to it. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [13] He, 2003, Serum amyloid A induces IL-8 secretion through a G protein-coupled receptor, FPRL1/LXA4R, Blood source

      The Results section, “SAA induces secretion of IL-8 by human neutrophils” (page unavailable), reports increased IL-8 and TNF-α production after SAA stimulation, but only minimal IL-1β secretion. The Discussion also describes prior evidence of IL-1β release. No passage in our copy supports the IL-23 part of the claim (searched: IL-23). (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    SAA induces IL33 gene expression in human monocytes and mouse macrophages.

    “It has been reported that SAA induces IL33 gene expression in human monocytes and mouse macrophages [27].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [27] Sun, 2014, Serum amyloid A induces interleukin-33 expression through an IRF7-dependent pathway, Eur. J. Immunol. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Exposure to ragweed pollen or airway uric acid induces extracellular release of IL-33 from epithelial cells.

    “Exposure to ragweed pollen [30] or airway uric acid [31] induced the extracellular release of IL-33 from epithelial cells.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [30] Haenuki, 2012, A critical role of IL-33 in experimental allergic rhinitis, J. Allergy Clin. Immunol. source
    • cites [31] Hara, 2014, Airway uric acid is a sensor of inhaled protease allergens and initiates type 2 immune responses in respiratory mucosa, J. Immunol. source

  • May combine two claims.

    Premisecitation

    DEX induces SAA expression on its own and synergistically increases LPS-induced SAA expression in THP-1 cells.

    “It has been shown that DEX induces SAA expression on its own and synergistically increases LPS-induced SAA expression in THP-1 cells [6].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [6] Bozinovski, 2012, Serum amyloid A opposes lipoxin A(4) to mediate glucocorticoid refractory lung inflammation in chronic obstructive pulmonary disease, Proc. Natl. Acad. Sci. USA source

  • May combine two claims.

    Premisecitation

    IL-33 is constitutively expressed at high levels and stored in the nucleus of endothelial and epithelial cells.

    “IL-33 is constitutive expressed at high levels and stored in the nucleus of endothelial and epithelial cells [28].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [28] Moussion, C., Ortega, N., and Girard, J.P. (2008). The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: A novel ‘alarmin’?. PLoS ONE, 3. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Allergen-induced IL-33 release is not associated with significant induction of IL33 mRNA in NHBE cells.

    “it was reported that allergen (fungal allergen Alternaria alternate extract)-induced IL-33 release was not associated with significant induction of IL33 mRNA in normal human bronchial epithelial (NHBE) cells [29].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [29] Hristova, 2016, Airway epithelial dual oxidase 1 mediates allergen-induced IL-33 secretion and activation of type 2 immune responses, J. Allergy Clin. Immunol. source

  • Classified as probably not a substantial claim.

    Premisecitation

    MAP kinases, NF-κB activation and PI3K are critical signaling components for expression of inflammatory cytokines.

    “MAP kinases, NF-κB activation and PI3K (phosphatidylinositol 3-kinase-Akt) are critical signaling components for the expression of inflammatory cytokines [22,23].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [22] Mercer, 2006, Emerging role of MAP kinase pathways as therapeutic targets in COPD, Int. J. Chron. Obstruct. Pulmon. Dis. source

      The Introduction and the section on cytokine stimulation of MAP kinase cascades link MAP kinases to cytokine expression and production. The cigarette-smoke section reports that MAP kinases can activate NF-κB, but does not establish NF-κB’s role in cytokine expression. The p38-inhibitors section mentions PI3K/Akt in relation to T-cell proliferation, not cytokine expression. Page numbers are unavailable in our copy. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [23] Liu, 2008, Cell-specific activation profile of extracellular signal-regulated kinase 1/2, Jun N-terminal kinase, and p38 mitogen-activated protein kinases in asthmatic airways, J. Allergy Clin. Immunol. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Several receptors including TLR2, TLR4, and P2X7 contribute to SAA-mediated signaling.

    “Previously, several receptors, including TLR2 [24], TLR4 [25], and P2X7 [26], have been shown to contribute to SAA-mediated signaling.”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [24] Cheng, 2008, Cutting edge: TLR2 is a functional receptor for acute-phase serum amyloid A, J. Immunol. source
    • cites [25] Sandri, 2008, Is serum amyloid A an endogenous TLR4 agonist?, J. Leukoc. Biol. source
    • cites [26] Niemi, 2011, Serum amyloid A activates the NLRP3 inflammasome via P2 × 7 receptor and a cathepsin B-sensitive pathway, J. Immunol. source

  • May combine two claims.

    Findingown data

    SAA induces IL-33 secretion in NCI-H292 cells, detectable at 0.1 μg/mL and maximal at 0.2 μg/mL.

    “The secretion of IL-33 was detected at a SAA concentration of 0.1 μg/mL and reached a maximal level at a SAA concentration of 0.2 μg/mL (Figure 2B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    SAA treatment increases IL33 mRNA expression after 2 h and decreases after 6 h in NCI-H292 cells.

    “After 2 h treatment with SAA, IL33 mRNA expression level was increased significantly and then decreased after 6 h (Figure 2C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    SAA does not induce LDH release or cell death in NCI-H292 cells, unlike NP-40.

    “When the cells were exposed to medium or to SAA, LDH activity was undetectable in the supernatants. On the contrary, when the cells were exposed to Nonidet P-40 (NP-40), a significant release of LDH was observed (Figure 2G).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    α-TLR2 or α-TLR4 reduces SAA-induced ERK1/2 and IκBα phosphorylation and completely blocks p38 phosphorylation in NCI-H292 cells.

    “Treatment with either α-TLR2 or α-TLR4 resulted in a reduction in SAA-induced ERK1/2 and IκBα phosphorylation. Interestingly, α-TLR2 or α-TLR4 completely blocked p38 phosphorylation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    SAA induces IL-33 release starting after 2 h, increasing until 6 h, and returning to normal after 12 h in NCI-H292 cells.

    “SAA induced IL-33 release started to increase after 2 h of incubation and increased further until the 6 h time point, returning to normal levels after 12 h (Figure 2D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Picroside II, but not dexamethasone, effectively inhibits SAA-induced IL-33 expression and secretion.

    “Picroside II, but not dexamethasone effectively inhibited SAA-induced IL-33 expression and secretion.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Pseudolysimachion rotundum var. subintegrum has been used as an Asian traditional medicine for inflammatory diseases.

    “Pseudolysimachion rotundum var. subintegrum (Plantaginaceae) has been used as an Asian traditional medicine for the treatment of inflammatory diseases [16].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Oh, 2006, Suppressive effect of verproside isolated from Pseudolysimachion longifolium on airway inflammation in a mouse model of allergic asthma, Int. Immunopharmacol. source

  • May combine two claims.

    Interpretationown data

    Picroside II is a potent inhibitor of SAA and IL-33 production, which is resistant to DEX.

    “our results clearly demonstrated that picroside II is a potent inhibitor of SAA and IL-33 production, which is resistant to DEX.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Picroside II and SAA used in experiments did not exhibit cytotoxic effects.

    “Picroside II and SAA used in this experiment did not exhibit any cytotoxic effect (Supplementary Figure S2).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisecitation

    YPL-001 derived from this herb has successfully completed phase-2a clinical trials in COPD patients.

    “YPL-001 (drug substance) derived from this herb has successfully completed phase-2a clinical trials in COPD patients (https://clinicaltrialsgov/).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites https://clinicaltrialsgov/

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Interpretationcitation

    Blocking IL-33 would be clinically beneficial for treating lung inflammation.

    “Thus, blocking IL-33 would be clinically beneficial for treating lung inflammation.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Extrahepatic SAA is mainly produced by monocytes/macrophages and plays a role in local responses to injury and inflammation.

    “Extrahepatic SAA is mainly produced by monocytes/macrophages and plays a role in local responses to injury and inflammation [20].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Meek, 1994, Human serum amyloid A genes are expressed in monocyte/macrophage cell lines, Am. J. Pathol.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Refractory COPD patients respond poorly to steroid treatment, exhibiting persistent airway inflammation.

    “However, refractory COPD patients respond poorly to steroid treatment, exhibiting persistent airway inflammation [5].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] Barnes, 2009, Glucocorticoid resistance in inflammatory diseases, Lancet source
24 of 24

  • The paper relies on this without support.

    The relationship between SAA and IL-33 secretion in airway epithelial cells has not been explored.

    “However, the relationship between SAA and IL-33 secretion in airway epithelial cells has not been explored.”

  • The paper relies on this without support.

    Little has been reported about whether picroside II is effective in treating steroid-resistant lung inflammation in COPD.

    “However, little has been reported about whether picroside II is effective in treating steroid-resistant lung inflammation in COPD.”

  • The paper relies on this without support.

    Picroside II is a major bioactive component of YPL-001.

    “Picroside II isolated from Pseudolysimachion rotundum var. subintegrum (Plantaginaceae) is a major bioactive component of YPL-001, which has completed phase-2a clinical trials in chronic obstructive pulmonary disease patients.”

  • The paper relies on this without support.

    NCI-H292 and THP-1 cell lines are valid models for human airway epithelial cells and monocytes.

    “Human airway epithelial cell line NCI-H292 and human monocytic leukemia cell line THP-1 were purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA).”

  • The paper relies on this without support.

    In vitro effects of picroside II on SAA/IL-33 are relevant to steroid-resistant lung inflammation in COPD patients.

    “These findings provide valuable information for the development of picroside II as an alternative therapeutic agent against steroid refractory lung inflammation in COPD.”
5 of 5

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Related

Authors
Lee, K., Choi, J., Choi, B. K., Gu, Y.-M., Ryu, H. W., Oh, S.-R., & Lee, H.-J.
Affiliations
Korea Research Institute of Bioscience and Biotechnology (KR)
Corresponding author
Lee, Hyun-Jun
ORCID
Venue
Molecules
Publisher
MDPI AG
Published
2019-05-27
Volume
24
Issue
10
Pages
2020
ISSN
1420-3049 (ISSN-L)
DOI
10.3390/molecules24102020
PMC
PMC6572537
OpenAlex
W2947131946
Semantic Scholar
f462161504adb6da378e21a980bb66970fcce66f
Cited by
11
References
37
Citations by year
2025: 3 · 2024: 2 · 2023: 2 · 2021: 2 · 2020: 1 · 2019: 1
FWCI
0.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecules (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • KRIBB Repository (submittedVersion)
Funders
National Research Foundation of Korea (2017R1A2B4008163)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
Keywords
picroside II, serum amyloid A, IL-33, glucocorticoid resistance, chronic obstructive pulmonary disease, MAPK signaling, NF-κB signaling, monocytes, plant-derived natural products
MeSH terms
Interleukin-33, Plantaginaceae, THP-1 Cells, Serum Amyloid A Protein, Cinnamates, Epithelial Cells, Glucocorticoids, Humans, Lipopolysaccharides, Lung, Monocytes, Transcription, Genetic, NF-kappa B, MAP Kinase Signaling System, Toll-Like Receptor 2, Toll-Like Receptor 4, Iridoid Glucosides

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