CoChat
Sign Up
Cited by 207Protein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase SignalingImmune Response and Inflammation

The Role of Mitogen-activated Protein Kinase Phosphatase-1 in the Response of Alveolar Macrophages to Lipopolysaccharide

Open access
Zhao, Qun, Shepherd, Edward G., Manson, Mary E., Nelin, Leif D., Sorokin, Andrey, Liu, Yusen·2005·Journal of Biological Chemistry
DOI 10.1074/jbc.m411760200
Open this paper in CoChat — free account

Abstract

Mitogen-activated protein (MAP) kinases are critical mediators of innate immune responses. In response to lipopolysaccharide (LPS), MAP kinases are rapidly activated and play an important role in the production of proinflammatory cytokines. Although a number of MAP kinase phosphatases (MKPs) have been identified, their roles in the control of cytokine production have not been well defined. In the present report, we investigated the role of MKP-1 in alveolar macrophages stimulated with LPS. We found that LPS triggered transient activation of three MAP kinase subfamilies, ERK, JNK, and p38, in both immortalized and primary murine alveolar macrophages. MKP-1 was rapidly induced by LPS, and its induction correlated with the dephosphorylation of these MAP kinases. Blocking MKP-1 with triptolide prolonged the activities of both JNK and p38 in immortalized alveolar macrophages. Stimulation of primary alveolar macrophages isolated from MKP-1-deficient mice with LPS resulted in a prolonged p38 phosphorylation compared with wild type alveolar macrophages. Accordingly, these MKP-1-deficient alveolar macrophages also mounted a more robust and rapid tumor necrosis factor alpha production than their wild type counterparts. Adenovirus-mediated MKP-1 overexpression significantly attenuated tumor necrosis factor alpha production in immortalized alveolar macrophages. Finally, MKP-1 was induced by a group of corticosteroids frequently prescribed for the treatment of inflammatory lung diseases, and the anti-inflammatory potencies of these drugs closely correlated with their abilities to induce MKP-1. Our studies indicated that MKP-1 plays an important role in dampening the inflammatory responses of alveolar macrophages. We speculate that MKP-1 may represent a novel target for therapeutic intervention of inflammatory lung diseases.

Integrity signals

Registry

Crossref · 10.1074/jbc.m411760200

Cites

37 of 37 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Proinflammatory stimuli such as LPS induce MKP-1 expression, creating a negative feedback loop that downregulates production of TNF-α, IL-1β, and IL-6.

    “Proinflammatory stimuli such as LPS also induce MKP-1 expression, creating a negative feedback loop that downregulates production of TNF-α, IL-1β, and IL-6 (Zhao et al., 2005).”

    From The Stressed CNS: When Glucocorticoids Aggravate Inflammation (2009) · cites this paper as Zhao et al., 2005

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Zhao, Q., Shepherd, E. G., Manson, M. E., Nelin, L. D., Sorokin, A., & Liu, Y.
Affiliations
  • The Ohio State University (US)
  • Medical College of Wisconsin (US)
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2005-03
Volume
280
Issue
9
Pages
8101-8108
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m411760200
OpenAlex
W2032124472
Cited by
207
References
37
Citations by year
2025: 5 · 2024: 4 · 2023: 4 · 2022: 7 · 2021: 6 · 2020: 10 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 5 · 2015: 4 · 2014: 11 · 2013: 6 · 2012: 15
FWCI
5.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL022563, R01HL22563)
  • National Institute of Allergy and Infectious Diseases (R01AI057798, R01 AI57798)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD043003)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
MKP-1, MAP kinase phosphatase, alveolar macrophages, lipopolysaccharide, ERK, JNK, p38 MAPK, MAP kinase dephosphorylation, triptolide, TNF-α, corticosteroids, anti-inflammatory activity, inflammatory lung disease, innate immunity
MeSH terms
Adenoviridae, Adrenal Cortex Hormones, Animals, Cell Line, Cells, Cultured, Enzyme Activation, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Inflammation, Kinetics, Lipopolysaccharides, Lung, Macrophages, Male, Mice, Inbred C57BL, Microscopy, Fluorescence, Phosphoprotein Phosphatases, Phosphorylation, RNA, Messenger, Time Factors, Blotting, Southern, Blotting, Northern, Blotting, Western, Macrophages, Alveolar, Protein Tyrosine Phosphatases, Immediate-Early Proteins, Cell Cycle Proteins, MAP Kinase Signaling System, p38 Mitogen-Activated Protein Kinases, Green Fluorescent Proteins, Mice, Dual Specificity Phosphatase 1, Protein Phosphatase 1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review