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Actions of exogenous and endogenous IL‐10 on glial responses to bacterial LPS/cytokines
Author(s) -
MolinaHolgado Francisco,
Grencis Richard,
Rothwell Nancy J.
Publication year - 2001
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/1098-1136(200102)33:2<97::aid-glia1009>3.0.co;2-n
Subject(s) - lipopolysaccharide , incubation , biology , endogeny , nitric oxide , prostaglandin e2 , tumor necrosis factor alpha , interleukin , cytokine , endocrinology , microbiology and biotechnology , medicine , immunology , biochemistry
The objective of this study was to investigate the actions of exogenous and endogenous IL‐10 on inflammatory responses of glia. Studies were conducted in primary, mixed glial cultures from C57BL/6 (wild‐type [WT]) and IL‐10‐deficient C57BL/6 (IL‐10 knockout [KO]) neonatal mice. Activation of cultures from WT mice by bacterial lipopolysaccharide (LPS, 10 ng/ml–10 μg/ml, 24 h), caused dose‐dependent increases in nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) release. In cultures from IL‐10 KO mice, LPS elicited markedly attenuated release of NO (approximately 4‐fold) and PGE 2 (approximately 17‐fold). In WT cultures, co‐incubation with IL‐10 (10 or 100 ng/ml, 24 h) inhibited the effects of LPS on release of NO (30%) and PGE 2 (40–50%). In cultures from IL‐10 KO mice, the addition of IL‐10 (10 or 100 ng/ml, 24 h) completely abolished LPS‐induced NO and PGE 2 release. LPS did, however, release of IL‐1β and TNF‐α in cultures from all animals. Co‐incubation of WT cultures with IL‐10 (1, 10, or 100 ng/ml, 24 h) dose‐dependently reduced the release of IL‐1β (by 0%, 15%, 75%, respectively). In cultures from IL‐10 KO mice, co‐incubation with IL‐10 (1, 10, or 100 ng/ml, 24 h) completely abolished LPS induced release of IL‐1β. Co‐incubation with IL‐10 (1, 10, 100 ng/ml) reduced, LPS‐induced TNF‐α release dose‐dependently in WT cultures (by 15%, 50% and 90%) and abolished LPS‐induced TNF‐α release in cells from IL‐10 KO mice. These results indicate that in glia from WT mice, exogenous IL‐10 attenuates LPS‐induces release of NO, PGE 2 , TNF‐α and IL‐1β. In contrast, mixed glial cultures from IL‐10 KO mice showed reduced responses to LPS, but increased sensitivity to exogenous IL‐10. GLIA 33:97–106, 2001. © 2001 Wiley‐Liss, Inc.