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A Key Role for Phosphoinositide 3‐Kinase in the Regulation of LPS‐ and TNF‐á‐induced CD44 Expression in Human Monocytic Cells
Author(s) -
Mishra Jyoti Prasad,
Mishra Sasmita,
Kumar Ashok
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.910.3
Subject(s) - pi3k/akt/mtor pathway , microbiology and biotechnology , proinflammatory cytokine , tumor necrosis factor alpha , cd44 , signal transduction , biology , cytokine , inflammation , cell , immunology , biochemistry
Alteration in the levels of CD44 expression on monocytic cells by endotoxins and immunoregulatory cytokines may modulate the migratory potential of immune cells to inflammatory sites and the development of immune responses. LPS and the proinflammatory cytokine, TNF‐α act as important regulators of CD44 expression in monocytic cells. We have previously demonstrated that LPS‐ and TNF‐α‐induced CD44 expression is regulated by two independent signaling pathways in human monocytic cells (Mishra et al. JBC, 2005). LPS‐induced CD44 expression is regulated by the JNK‐activated Egr‐1 whereas CaMK‐II‐activated AP‐1 regulates TNF‐α‐induced CD44 expression. In this study, we show that PI 3‐kinase (PI3K) constitutes a key downstream component of both the signaling pathways involved in the regulation of LPS‐ and TNF‐α‐induced CD44 expression. Our results suggest that the JNK‐activated PI3K regulates LPS‐induced CD44 expression through the activation of Egr‐1 whereas TNF‐α induces CD44 expression by a distinct CaMK‐II‐activated PI3K through the activation of AP‐1. Taken together, our results suggest a critical involvement of PI3K in the regulation of LPS‐ and TNF‐α‐induced CD44 expression and hence may represent a potential therapeutic target for inhibiting CD44 expression and consequent CD44‐mediated cell migration, inflammation and autoimmune disorders. This work was supported by NSERC, Canada and OGSST.