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Interleukin‐4, interleukin‐10, and interleukin‐1‐receptor antagonist but not transforming growth factor‐β induce ramification and reduce adhesion molecule expression of rat microglial cells
Author(s) -
Wirjatijasa Florentina,
Dehghani Faramarz,
Blaheta Roman A.,
Korf HorstWerner,
Hailer Nils P.
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10254
Subject(s) - tumor necrosis factor alpha , interleukin , biology , transforming growth factor , secretion , cytokine , cell adhesion molecule , microglia , microbiology and biotechnology , receptor antagonist , receptor , astrocyte , immunology , endocrinology , inflammation , antagonist , central nervous system , biochemistry
The activity of microglial cells is strictly controlled in order to maintain central nervous system (CNS) immune privilege. We hypothesized that several immunomodulatory factors present in the CNS parenchyma, i.e., the Th2‐derived cytokines interleukin (IL)‐4 and IL‐10, interleukin‐1‐receptor‐antagonist (IL‐1‐ra), or transforming growth factor (TGF)‐β can modulate microglial morphology and functions. Microglial cells were incubated with IL‐4, IL‐10, IL‐1‐ra, TGF‐β, or with astrocyte conditioned media (ACM) and were analyzed for morphological changes, expression of intercellular adhesion molecule (ICAM)‐1, and secretion of IL‐1β or tumor necrosis factor (TNF)‐α. Whereas untreated controls showed an amoeboid morphology both Th2‐derived cytokines, IL‐1‐ra, and ACM induced a morphological transformation to the ramified phenotype. In contrast, TGF‐β‐treated microglial cells showed an amoeboid morphology. Even combined with the neutralizing antibodies against IL‐4, IL‐10, or TGF‐β ACM induced microglial ramification. Furthermore, ACM did not contain relevant amounts of IL‐4 and IL‐10, as measured by enzyme‐linked immunosorbent assay (ELISA). Flow cytometry showed that lipopolysaccharide (LPS)‐induced ICAM‐1‐expression on microglial cells was strongly suppressed by ACM, significantly modulated by IL‐4, IL‐10, or IL‐1‐ra, but not influenced by TGF‐β. The LPS‐induced secretion of IL‐1β and TNF‐α was only reduced after application of ACM, whereas IL‐4 or IL‐10 did not inhibit IL‐1β‐ or TNF‐α secretion. TGF‐β enhanced IL‐1β‐ but not TNF‐α secretion. In summary, we demonstrate that IL‐4, IL‐10, and IL‐1‐ra induce microglial ramification and reduce ICAM‐1‐expression, whereas the secretion of proinflammatory cytokines is not prevented. TGF‐β has no modulating effects. Importantly, unidentified astrocytic factors that are not identical with IL‐4, IL‐10, or TGF‐β possess strong immunomodulatory properties. © 2002 Wiley‐Liss, Inc.