The immunomodulating neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) suppresses LPS-stimulated TLR4 with IRAK-M in macrophages.
Since alpha-MSH suppresses endotoxin-induced inflammation by innate immunity, it is possible that alpha-MSH can suppress the interface between innate and adaptive immunity mediated by TLR4-stimulated macrophages. Endotoxin-stimulated macrophages treated with alpha-MSH are suppressed in nitric oxide and IL-12p70 production, and cannot enhance antigen-stimulated IFN-gamma production by Th1 cells. In macrophages treated with alpha-MSH, the inhibitory molecule IRAK-M is bound to IRAK-1, the proximal intracellular signal molecule of endotoxin-bound TLR4. These results further demonstrate the dynamic contribution of the nervous system, and the role of alpha-MSH in modulating the innate and adaptive immune interface in an inflammatory response.
Taylor
A W
AW
Schepens Eye Research Institute and The Department of Ophthalmology, Harvard Medical School, Boston, MA, USA. awtaylor@vision.eri.harvard.edu
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D047468:Immunoprecipitation / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D015213:Neuroimmunomodulation; D009569:Nitric Oxide / Q000378:metabolism; D010052:Ovariectomy / Q000379:methods; D011494:Protein Kinases / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D013997:Time Factors; D051197:Toll-Like Receptor 4; D000521:alpha-MSH / Q000494:pharmacology*
D008070:Lipopolysaccharides; D011971:Receptors, Immunologic; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D018664:Interleukin-12; D009569:Nitric Oxide; D000521:alpha-MSH; D007371:Interferon-gamma; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases; C507772:Irak3 protein, mouse