Ligation of microglial CD40 results in p44/42 mitogen-activated protein kinase-dependent TNF-alpha production that is opposed by TGF-beta 1 and IL-10 - PubMed (original) (raw)

. 1999 Dec 15;163(12):6614-21.

Affiliations

PMID: 10586056

Ligation of microglial CD40 results in p44/42 mitogen-activated protein kinase-dependent TNF-alpha production that is opposed by TGF-beta 1 and IL-10

J Tan et al. J Immunol. 1999.

Abstract

Recently, it has been demonstrated that the CD40 receptor is constitutively expressed on cultured microglia at low levels. Ligation of CD40 by CD40 ligand on these cells results in microglial activation, as measured by TNF-alpha production and neuronal injury. However, the intracellular events mediating this effect have yet to be investigated. We report that ligation of microglial CD40 triggers activation of p44/42 mitogen-activated protein kinase (MAPK). This effect is evident 30 min posttreatment, and progressively declines thereafter (from 30 to 240 min). Phosphorylated p38 MAPK is not observed in response to ligation of microglial CD40 across the time course examined. Inhibition of the upstream activator of p44/42 MAPK, mitogen-activated protein/extracellular signal-related kinase kinase 1/2, with PD98059, decreases phosphorylation of p44/42 MAPK and significantly reduces TNF-alpha release following ligation of microglial CD40. Furthermore, cotreatment of microglial cells with CD40 ligand and TGF-beta1 or IL-10, or both, inhibits CD40-mediated activation of p44/42 MAPK and production of TNF-alpha in a statistically interactive manner. Taken together, these data show that ligation of microglial CD40 triggers TNF-alpha release through the p44/42 MAPK pathway, an effect that can be opposed by TGF-beta1 and IL-10.

PubMed Disclaimer

Cited by

Heterogeneous expression of the triggering receptor expressed on myeloid cells-2 on adult murine microglia.
Schmid CD, Sautkulis LN, Danielson PE, Cooper J, Hasel KW, Hilbush BS, Sutcliffe JG, Carson MJ. Schmid CD, et al. J Neurochem. 2002 Dec;83(6):1309-20. doi: 10.1046/j.1471-4159.2002.01243.x. J Neurochem. 2002. PMID: 12472885 Free PMC article.
MicroRNA-124 regulates the expression of MEKK3 in the inflammatory pathogenesis of Parkinson's disease.
Yao L, Ye Y, Mao H, Lu F, He X, Lu G, Zhang S. Yao L, et al. J Neuroinflammation. 2018 Jan 12;15(1):13. doi: 10.1186/s12974-018-1053-4. J Neuroinflammation. 2018. PMID: 29329581 Free PMC article.
Blueberry opposes beta-amyloid peptide-induced microglial activation via inhibition of p44/42 mitogen-activation protein kinase.
Zhu Y, Bickford PC, Sanberg P, Giunta B, Tan J. Zhu Y, et al. Rejuvenation Res. 2008 Oct;11(5):891-901. doi: 10.1089/rej.2008.0757. Rejuvenation Res. 2008. PMID: 18789000 Free PMC article.
Microglia as liaisons between the immune and central nervous systems: functional implications for multiple sclerosis.
Carson MJ. Carson MJ. Glia. 2002 Nov;40(2):218-231. doi: 10.1002/glia.10145. Glia. 2002. PMID: 12379909 Free PMC article. Review.
CD45RB is a novel molecular therapeutic target to inhibit Abeta peptide-induced microglial MAPK activation.
Zhu Y, Hou H, Nikolic WV, Ehrhart J, Rrapo E, Bickford P, Giunta B, Tan J. Zhu Y, et al. PLoS One. 2008 May 14;3(5):e2135. doi: 10.1371/journal.pone.0002135. PLoS One. 2008. PMID: 18478117 Free PMC article.

Ligation of microglial CD40 results in p44/42 mitogen-activated protein kinase-dependent TNF-alpha production that is opposed by TGF-beta 1 and IL-10 - PubMed (original) (raw)