Interleukin-1alpha-induced chemokines in mouse granulosa cells: impact on keratinocyte chemoattractant chemokine, a CXC subfamily.
IL-1 is well known to be involved in the immune system and have a role in ovarian inflammation as well as exhibiting inhibitory effects on steroidogenesis and folliculogenesis. Because multiple aspects of ovarian function have also been shown to involve cytokine/chemokine networks, IL-1alpha-induced chemokine gene expression in mouse granulosa cells was investigated. Granulosa cells from immature mice at 28 d of age were cultured with IL-1alpha (10 ng/ml). IL-1alpha induced abundantly and specifically keratinocyte chemoattractant (KC) chemokine, a CXC subfamily. KC chemokine mRNA and protein were increased 1-2 h after IL-1alpha and then gradually decreased. The KC promoter (-701/+30) containing three nuclear factor (NF)-kappaB sites was fully responsive to IL-1alpha, whereas deletions and mutants of the NF-kappaB sites lowered the responsiveness to IL-1alpha. The proximal NF-kappaB site (-69/-59) played a critical role in regulating IL-1alpha-induced KC chemokine promoter activity. Overexpression of the inhibitor of NF-kappaB (IkappaB) blocked KC promoter activity induced by IL-1alpha, whereas overexpression of p65, a component of NF-kappaB, increased promoter activity and mRNA of KC chemokine. In addition, FSH did not affect NF-kappaB signaling or IL-1alpha-induced KC chemokine promoter activity. Within 1-3 h after ip injection of lipopolysaccharide (100 mug/mouse), a product known to stimulate release of IL-1, KC chemokine was localized in the ovary to granulosa cells as well as the thecal-interstitial layer. The results of this study indicate that KC gene is a chemokine induced acutely by IL-1alpha via NF-kappaB signaling in mouse granulosa cells.
Son
Deok-Soo
DS
Center of Reproductive Sciences, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, Kansas 66160-7417, USA. dson@kumc.edu
Roby
Katherine F
KF
D000818:Animals; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism* / Q000502:physiology; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002630:Chemotactic Factors / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D006107:Granulosa Cells / Q000502:physiology*; D053582:Interleukin-1alpha / Q000494:pharmacology* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000502:physiology; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D013997:Time Factors; D014018:Tissue Distribution
C499706:CXCL2 protein, human; C499707:CXCL3 protein, human; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D004731:Endotoxins; D053582:Interleukin-1alpha; D016328:NF-kappa B; C074302:keratinocyte-derived chemokines