Gene expressions of lipopolysaccharide receptors, toll-like receptors 2 and 4, are differently regulated in mouse T lymphocytes

Toll-like receptors (TLRs) are a family of mammalian proteins homologous to Drosophila Toll. Human TLR2 was shown to mediate the responsiveness to lip opolysaccharide (LPS). On the other hand, gene mutations of mouse TLR4 (mTL R4) in LPS-hyporesponsive strains have suggested that mTLR4 is essential fo r LPS-signaling in mice, but the role of mTLR2 has not been explored. This report describes molecular cloning of the mTLR2 cDNA, Overexpression of mTL R2 and mouse CD14 conferred LPS-inducibility of c-Jun N-terminal kinase pho sphorylation and nuclear factor-KB activation to COS7 cells, suggesting tha t mTLR2 is a signaling receptor for LPS, Both mTLR2 and mTLR4 genes were ex pressed in T cells. Treatment with anti-CD3 epsilon, PMA plus ionomycin, or interleukin-2 (IL-2)/IL-15 increased mTLR2 but not mTLR4 messenger RNA (mR NA) in some T cell lines. Specific inhibitors of mitogen-activated extracel lular signal-regulated kinase and fusion protein 38 (p38) kinase inhibited mTLR2 mRNA up-regulation by PMA plus ionomycin, This suggests that extracel lular signal-regulated kinase and p38 kinase pathways were involved. Additi onally, LPS treatment of EL-4 cell line decreased IL-4 gene expression. Our results indicate that both mTLR2 and mTLR4 are involved in LPS signaling, but their expressions are regulated differently in T cells, and that LPS ma y directly affect T-cell functions by binding to TLRs. (C) 2000 by The Amer ican Society of Hematology.