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Leptin is an adipocyte-secreted hormone and itsplasma levels correlate with total body fat mass, however, italso plays a regulatory role in immunity, inflammation, andhematopoiesis. Chemokine is known as a chemoattractantcytokine in inflammatory reaction, but its role in leptinreaction has not been well studied. In this study, the directeffect of leptin on the expression of chemokine mRNAs andlipopolysaccharide (LPS)-induced chemokine KC mRNA inmouse peritoneal macrophages was investigated. Leptin didnot induce the expression of lymphotactin, RANTES, eotaxin,MIP-1β, MIP-1α, MIP-2, MCP-1, IP-10, TCA-3, and KCmRNA in mouse peritoneal macrophages, and had no directeffect on the expression of these LPS-induced chemokinemRNAs except KC mRNA. The synergistic effect of leptinon the expression of LPS-induced KC mRNA occurred late inthe time course of response to LPS. The increased expressionsof Ob-Rb mRNA and leptin receptor protein were detectedduring the LPS treatment. Leptin produced a substantialincrease in the stability of the LPS-induced KC mRNA, andthe synergistic effect of leptin on LPS-induced KC mRNAexpression was further augmented by cycloheximide (CHX).Pyrrolidine dithiocarbamate (PDTC) did not block the synergisticeffect of leptin on LPS-induced KC mRNA expression inmouse peritoneal macrophages. These data suggest that althoughleptin has no direct effect on the expression of lymphotactin,RANTES, eotaxin, MIP-1β, MIP-1α, MIP-2, MCP-1, IP-10,TCA-3, and KC mRNA in mouse peritoneal macrophages, thesynergistic effect of leptin on the expression of LPS-inducedKC mRNA has the possibility that LPS might induce theexpression of the Ob-Rb receptor or an unknown gene(s) thatsensitizes macrophages to the synergistic function of leptin.Therefore, further studies are necessary to examine leptin as aregulatory factor of chemokine production.

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