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Role of interleukin‐6 and soluble IL‐6 receptor in region‐specific induction of astrocytic differentiation and neurotrophin expression
Author(s) -
März Pia,
Heese Klaus,
DimitriadesSchmutz Beatrice,
RoseJohn Stefan,
Otten Uwe
Publication year - 1999
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/(sici)1098-1136(199905)26:3<191::aid-glia1>3.0.co;2-#
Subject(s) - biology , neurotrophin , astrocyte , nerve growth factor , neuroglia , neuroscience , neurotrophin 3 , microbiology and biotechnology , receptor , central nervous system , cerebellum , neurotrophic factors , brain derived neurotrophic factor , biochemistry
Increasing evidence supports an essential role for interleukin‐6 (IL‐6) in the development, differentiation, as well as de‐ and re‐generation of neurons in the central nervous system (CNS). Both IL‐6 and its specific receptor (IL‐6R) are expressed on neurons and glial cells including astrocytes. In this study, we have analyzed the responses of primary rat astrocytes of various brain regions to IL‐6 with respect to morphological changes and neurotrophin expression. Since IL‐6 alone failed to initiate effects on astrocytes, we have examined whether the soluble IL‐6R (sIL‐6R) can modulate the responsiveness of to IL‐6 in these cells. For this purpose, we used a highly active fusion protein of IL‐6 and sIL‐6R, which is designated Hyper‐IL‐6 (H‐IL‐6). We show that treatment of cultured astrocytes with Hyper‐IL‐6 promotes region‐specific morphological changes of GFAP‐positive astrocytes from typical stellate‐ to fibrous‐like cells. In addition, we find that Hyper‐IL‐6 induces expression of neurotrophins (NTs) of the nerve growth factor (NGF)‐family in a dose‐dependent manner. Interestingly, astrocytes of various brain regions show differing patterns of cytokine‐induced NT expression: NGF is maximally induced in cortex and hippocampus, NT‐3 in hippocampus, and NT‐4/5 in cortex and cerebellum. In summary, our results indicate that IL‐6 in conjunction with sIL‐6R regulates specific neurotrophin expression in astrocytes in a brain region dependent manner. Thus, the IL‐6 system provides a local supply of neurotrophins that participate in diverse CNS functions such as protection of neurons from insults, neuronal survival, and neuro‐immune responses. GLIA 26:191–200, 1999. © 1999 Wiley‐Liss, Inc.