title: Fever induction by systemic stimulation with macrophage-activating lipopeptide-2 depends upon TLR2 but not CD36.
abstract: This study was designed to test the responses of TLR2-knockout mice (TLR2-KO) and wild- type mice (C57/BL-6), and of CD36 deficient spontaneously hypertensive rats (SHR) and their genetic controls [Wistar Kyoto (WKY) rats] to systemic stimulations with the TLR2/6 agonist MALP-2 and the TLR4 agonist LPS. Fever and formation of TNF-α and IL-6 induced by intraperitoneal injections of MALP-2 (1000 µg/kg) were completely blunted in TLR2-KO, while LPS (100 µg/kg)-induced responses were not abolished in these animals. In SHR lacking CD36, a reduction of fever was observed in response to MALP-2 (100 µg/kg), but LPS-fever was even more attenuated in SHR when compared with WKY controls. Concentrations of circulating IL-6 tended to be lower in SHR after stimulation with both pyrogens. However, the IL-6-mediated activation of the transcription factor STAT3 in the brain was identical in both strains, indicating that the brain-controlled inflammatory response to MALP-2 (and LPS) is not impaired in the absence of CD36. In addition, stimulation of peritoneal macrophages with LPS and MALP-2 (10 µg/ml) caused the appearance of similar concentrations of bioactive cytokines in the supernatants from cells of both rat strains. These results demonstrate that TLR2 is essential for the manifestation of MALP-2, but not LPS-induced inflammatory responses. A moderate participation of CD36 in MALP-2-induced sickness- and cytokine-responses can not be ruled out but is unlikely as LPS-induced inflammatory responses were also attenuated in SHR.
authors: Institut für Veterinär-Physiologie und -Biochemie, Justus-Liebig- Universität Giessen, Giessen, Germany.
authors: Janina
authors: J
authors: Welsch
authors: Thomas
authors: T
authors: Hübschle
authors: Jolanta
authors: J
authors: Murgott
authors: Carsten
authors: C
authors: Kirschning
authors: Christoph
authors: C
authors: Rummel
authors: Rüdiger
authors: R
authors: Gerstberger
authors: Joachim
authors: J
authors: Roth
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005334:Fever / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D055666:Lipopeptides / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D051195:Toll-Like Receptor 2 / Q000819:agonists* / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000819:agonists; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D015850:Interleukin-6; D055666:Lipopeptides; D008070:Lipopolysaccharides; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C106335:macrophage stimulatory lipopeptide 2