Constitutive and LPS-Induced Expression of MCP-1 and IL-8 by Human Uveal Melanocytes In Vitro and Relevant Signal Pathways
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PURPOSE: Melanocytes are one of the major cellular components in the uvea. Interleukin-8/CXCL8 and monocyte chemoattractant protein-1 (MCP-1/CCL2) are the two most important proinflammatory chemokines. We studied the constitutive and lipopolysaccharide (LPS)-induced expression of IL-8 and MCP-1 in cultured human uveal melanocytes (UM) and explored the relevant signal pathways. METHODS: Conditioned media and cells were collected from UM cultured in medium with and without stimulation of LPS. Interleukin-8 and MCP-1 proteins and mRNAs were measured using an ELISA kit and RT-PCR, respectively. Nuclear factor (NF)-κB in nuclear extracts and phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases1/2 (ERK1/2), and c-Jun N-terminal kinase1/2 (JNK1/2) in cells cultured with and without LPS were measured by ELISA kits. Inhibitors of p38 (SB203580), ERK1/2 (UO1026), JNK1/2 (SP600125), and NF-κB (BAY11-7082) were added to the cultures to evaluate their effects. RESULTS: Low levels of IL-8 and MCP-1 proteins were detected in the conditioned media in UM cultured without serum. Lipopolysaccharide (0.01-1 μg/mL) increased IL-8 and MCP-1 mRNAs and proteins levels in a dose- and time-dependent manner, accompanied by a significant increase of phosphorylated JNK1/2 in cell lysates and NF-κB in nuclear extracts. Nuclear factor-κB and JNK1/2 inhibitors significantly blocked LPS-induced expression of IL-8 and MCP-1. CONCLUSIONS: This is the first report on the expression and secretion of chemokines by UM. The data suggest that UM may play a role in the pathogenesis of ocular inflammatory diseases.
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Uveal melanocytes release MCP-1, IL-6 and IL-8 after an inflammatory stimulation by LPS or IL-1β that is accompanied by JNK1/2 upregulation and can also be attenuated by p38 inhibition.
“Uveal melanocytes release MCP-1, IL-6 and IL-8 after an inflammatory stimulation by LPS or IL-1β that is accompanied by JNK1/2 upregulation and can also be attenuated by p38 inhibition [ 182 , 183 ]”
From MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges (2023) · cites this paper as [182]
The Discussion (page not supplied) reports that LPS increases MCP-1 and IL-8 secretion by human uveal melanocytes and prominently increases JNK1/2 activity. The inhibitor results (page not supplied) show that p38 inhibition reduces MCP-1 secretion, but does not significantly reduce IL-8 secretion. This paper does not report LPS- or IL-1β-induced release of all three named molecules; it mentions IL-1β-induced IL-6 secretion only as a previous study. (LLM, conf=0.90)
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References 75 · Cited by 36
Research works printed but not linked: 4
- Hu DN, McCormick SA, Orlow SJ, Rosemblat S, Lin AY, Wo K. Melanogenesis in cultured human uveal melanocytes. Invest Ophthalmol Vis Sci. 1995;36:931-938.
- Cavicchio VA, Pru JK, Davis BS, Davis JS, Rueda BR, Townson DH. Secretion of monocyte chemoattractant protein-1 by endothelial cells of the bovine corpus luteum: regulation by cytokines but not prostaglandin F2alpha. Endocrinology. 2002;143:3582-3589.
- Gawaz M, Neumann FJ, Dickfeld T, et al. Activated platelets induce monocyte chemotactic protein-1 secretion and surface expression of intercellular adhesion molecule-1 on endothelial cells. Circulation. 1998;98:1164-1171.
- Strunnikova NV, Barb J, Sergeev YV, et al. Loss-of-function mutations in Rab escort protein 1 (REP-1) affect intracellular transport in fibroblasts and monocytes of choroideremia patients. PLoS One. 2009;4:e8402.
- Authors
- Hu, D.-N., Bi, M., Zhang, D. Y., Ye, F., McCormick, S. A., & Chan, C.-C.
- Affiliations
- New York Eye and Ear Infirmary (US)
- Mount Sinai Hospital (US)
- Mount Sinai Health System (US)
- National Institutes of Health (US)
- Corresponding author
- Hu, Dan-Ning
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2014-09-11
- Volume
- 55
- Issue
- 9
- Pages
- 5760
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC4161485
- OpenAlex
- W2315047790
- Cited by
- 36
- References
- 75
- Citations by year
- 2025: 5 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 1
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Touro Scholar (Touro College) (submittedVersion)
- Funders
- New York Eye and Ear Infirmary of Mount Sinai
- Topics
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Health Sciences › Medicine › Ophthalmology › Ocular Oncology and Treatments
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- uveal melanocytes, interleukin-8, MCP-1, chemokine expression, lipopolysaccharide, NF-κB signaling, JNK1/2 signaling, p38 MAPK, ERK1/2, ocular inflammation, uvea
- MeSH terms
- Cells, Cultured, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Humans, Lipopolysaccharides, Melanocytes, RNA, Messenger, Uvea, Signal Transduction, Interleukin-8, NF-kappa B, Chemokine CCL2, Mitogen-Activated Protein Kinase Kinases, Protein Kinase Inhibitors
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