TLR2 expression in astrocytes is induced by TNF-α- and NF-κB-dependent pathways

Nirmal K. Phulwani, Nilufer Esen, Mohsin Md Syed, Tammy L Kielian

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Astrocytes participate in CNS innate immune responses as evident by their ability to produce a wide array of inflammatory mediators upon exposure to diverse stimuli. Although we have established that astrocytes use TLR2 to signal inflammatory mediator production in response to Staphylococcus aureus, a common etiological agent of CNS infections, the signal transduction pathways triggered by this pathogen and how TLR2 expression is regulated remain undefined. Three disparate inhibitors that block distinct steps in the NF-κB pathway, namely SC-514, BAY 11-7082, and caffeic acid phenethyl ester, attenuated NO, TNF-α, and CXCL2 release from S. aureus-activated astrocytes. Among these proinflammatory mediators, autocrine/paracrine TNF-α was pivotal for augmenting TLR2 expression, since receptor levels were not elevated in astrocytes isolated from TNF-α knockout mice upon bacterial exposure. Since TLR2 is critical for signaling astrocytic cytokine production in response to S. aureus, we evaluated the effect of TNF-α loss on proinflammatory mediator release. Interestingly, among the molecules assayed, only NO production was significantly attenuated in TNF-α knockout astrocytes compared with wild-type cells. Similar results were obtained following LPS treatment, suggesting that TNF-α is an important regulator of astrocytic TLR2 expression and NO release in response to diverse microbial stimuli. In addition, NF-κB inhibitors attenuated TNF-α-induced TLR2 expression in astrocytes. Overall, this study suggests that two important anti-bacterial effector molecules, TLR2 and NO, are regulated, in part, by NF-κB- dependent autocrine/paracrine effects of TNF-α in astrocytes.

Original languageEnglish (US)
Pages (from-to)3841-3849
Number of pages9
JournalJournal of Immunology
Volume181
Issue number6
StatePublished - Sep 15 2008

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Astrocytes
Staphylococcus aureus
Innate Immunity
Knockout Mice
Signal Transduction
Cytokines
Infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

TLR2 expression in astrocytes is induced by TNF-α- and NF-κB-dependent pathways. / Phulwani, Nirmal K.; Esen, Nilufer; Syed, Mohsin Md; Kielian, Tammy L.

In: Journal of Immunology, Vol. 181, No. 6, 15.09.2008, p. 3841-3849.

Research output: Contribution to journalArticle

Phulwani, Nirmal K. ; Esen, Nilufer ; Syed, Mohsin Md ; Kielian, Tammy L. / TLR2 expression in astrocytes is induced by TNF-α- and NF-κB-dependent pathways. In: Journal of Immunology. 2008 ; Vol. 181, No. 6. pp. 3841-3849.
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