RRC ID 41682
Author Murakami Y, Akahoshi T, Kawai S, Inoue M, Kitasato H.
Title Antiinflammatory effect of retrovirally transfected interleukin-10 on monosodium urate monohydrate crystal-induced acute inflammation in murine air pouches.
Journal Arthritis Rheum.
Abstract OBJECTIVE:To investigate the role of interleukin-10 (IL-10) in the inflammatory response, the antiinflammatory effect of retrovirally transfected IL-10 was evaluated both in vitro and in vivo.
METHODS:A recombinant retrovirus containing the murine IL-10 gene was constructed using the pLXSN vector and was designated as LXSN-IL-10. Murine IL-10 was introduced into embryonic C57BL/6J fibroblast cells using LXSN-IL-10 to create C57-IL-10 cells. The effect of IL-10 in the culture supernatant of these cells was then evaluated by determining changes in the production of tumor necrosis factor alpha (TNFalpha), macrophage inflammatory protein 1alpha (MIP-1alpha), and MIP-1beta by macrophages. The antiinflammatory effect of C57-IL-10 cells was also investigated using an in vivo model of monosodium urate monohydrate (MSU) crystal-induced acute inflammation.
RESULTS:The IL-10 gene transcript and its product were detected by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The level of IL-10 in the culture supernatant of C57-IL-10 cells was estimated to be 50 ng/ml. The culture supernatant of these cells exerted the biologic activity of IL-10, showing inhibition of TNFalpha, MIP-1alpha, and MIP-1beta production by macrophages. Injection of C57-IL-10 cells into murine air pouches significantly inhibited MSU crystal-induced cellular infiltration (P < 0.01) and production of the mouse CXC chemokine KC (P < 0.05). These findings were consistent with the results obtained by the injection of recombinant human IL-10 into air pouches.
CONCLUSION:In this murine air pouch model of MSU crystal-induced inflammation, IL-10 seemed to inhibit the recruitment of neutrophils at least partly by suppressing KC production. These findings seem to suggest that IL-10 gene therapy may be useful for inflammatory diseases.
Volume 46(9)
Pages 2504-13
Published 2002-9
DOI 10.1002/art.10468
PMID 12355499
MeSH Air Animals Anti-Inflammatory Agents / pharmacology* Cell Line Chemokine CXCL1 Chemokines / biosynthesis Chemokines / genetics Chemokines, CXC / biosynthesis Chemotactic Factors / biosynthesis Crystallization Cytokines / biosynthesis Cytokines / genetics Embryo, Mammalian Gene Expression Gene Transfer Techniques Humans Injections, Subcutaneous Intercellular Signaling Peptides and Proteins / biosynthesis Interleukin-10 / genetics Interleukin-10 / pharmacology* Macrophages, Peritoneal / drug effects Macrophages, Peritoneal / metabolism Male Mice Mice, Inbred C57BL Recombinant Proteins / pharmacology Retroviridae / genetics* Transfection* Uric Acid / chemistry* Uric Acid / pharmacology
Times Cited 28
Human and Animal Cells