Journal article
IL-10 Is a Central Regulator of Cyclooxygenase-2 Expression and Prostaglandin Production
The Journal of immunology (1950), Vol.166(4), pp.2674-2680
02/15/2001
DOI: 10.4049/jimmunol.166.4.2674
PMID: 11160331
Abstract
IL-10 is a potent anti-inflammatory and immune regulatory cytokine. IL-10(-/-) mice produce exaggerated amounts of inflammatory cytokines when stimulated with LPS, indicating that endogenous IL-10 is a central regulator of inflammatory cytokine production in vivo. PGs are lipid mediators that are also produced in large amounts during the inflammatory response. To study the role of IL-10 in the regulation of PG production during the acute inflammatory response, we evaluated LPS-induced cyclooxygenase (COX) expression and PG production in wild-type (wt) and IL-10(-/-) mice. LPS-induced PGE(2) production from IL-10(-/-) spleen cells was 5.6-fold greater than that from wt spleen cells. LPS stimulation resulted in the induction of COX-2 mRNA and protein in both wt and IL-10(-/-) spleen cells; however, the magnitude of increase in COX-2 mRNA was 5.5-fold greater in IL-10(-/-) mice as compared with wt mice. COX-1 protein levels were not affected by LPS stimulation in either wt or IL-10(-/-) mice. Neutralization of IFN-gamma, TNF-alpha, or IL-12 markedly decreased the induction of COX-2 in IL-10(-/-) spleen cells, suggesting that increased inflammatory cytokine production mediates much of the COX-2 induction in IL-10(-/-) mice. Treatment of IL-10(-/-) mice with low doses of LPS resulted in a marked induction of COX-2 mRNA in the spleen, whereas wt mice had minimal expression of COX-2 mRNA. These findings indicate that, in addition to IL-10's central role in the regulation of inflammatory cytokines, endogenous IL-10 is an important regulator of PG production in the response to LPS.
Details
- Title: Subtitle
- IL-10 Is a Central Regulator of Cyclooxygenase-2 Expression and Prostaglandin Production
- Creators
- Daniel J BergJuan ZhangDina M LauricellaSteven A Moore
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.166(4), pp.2674-2680
- DOI
- 10.4049/jimmunol.166.4.2674
- PMID
- 11160331
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 02/15/2001
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Internal Medicine
- Record Identifier
- 9984047707402771
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