MyD88 and Src are differentially regulated in Kupffer cells of males and proestrus females following hypoxia.
Hypoxia produces sex dimorphic immune responses in males and proestrus females. Because Kupffer cells are the major source of proinflammatory cytokines, studies were conducted to discern IL-6 production in mouse Kupffer cells following hypoxia. Hypoxia enhances TLR4 expression in Kupffer cells irrespective of sex. However, MyD88 and Src expression in Kupffer cells decreased significantly after hypoxia in proestrus females, whereas Src protein expression and phosphorylation increased in males in concurrence with differences in IL-6 production. 17beta-estradiol administration elevated MyD88 and Src expression in males to levels in normoxic proestrus females. Administration of Src inhibitor in hypoxic males prevented increased IL-6 production. Thus, differential regulation of MyD88 and Src in males and females plays an important role in sex-specific immune response following hypoxia.
Zheng
Rui
R
Center for Surgical Research, Department of Surgery, University of Alabama at Birmingham, AL 35294-0019, USA.
Pan
George
G
Thobe
Bjoern M
BM
Choudhry
Mashkoor A
MA
Matsutani
Takeshi
T
Samy
T S Anantha
TS
Kang
Shih-Ching
SC
Bland
Kirby I
KI
Chaudry
Irshad H
IH
D000818:Animals; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D000860:Hypoxia / Q000276:immunology*; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis; D007728:Kupffer Cells / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011359:Proestrus / Q000276:immunology*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012727:Sex Characteristics; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; D015850:Interleukin-6; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011720:Pyrazoles; D011743:Pyrimidines; D051197:Toll-Like Receptor 4; D004958:Estradiol; D019061:src-Family Kinases