Upregulation of HO-1 Attenuates LPS-Stimulated Proinflammatory Responses Through Downregulation of p38 Signaling Pathways in Rat Ovary
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Heme oxygenase-1 (HO-1) plays a key role in the regulation of the inflammatory response. However, the specific mechanism underlying the anti-inflammatory role of HO-1 in the reproductive system is unclear. The aim of this study was to evaluate the role of the mechanism of HO-1 in the regulation of the inflammatory response stimulated by lipopolysaccharide (LPS) in rat ovary. LPS-stimulated inflammatory models were established. Rats were pretreated with HO-1 activator (hemin) or inhibitor (ZnPP) before LPS stimulation, and we evaluated the expression of HO-1 by real-time PCR and Western blot. The messenger RNA (mRNA) expression and secretion of IL-1β and IL-6 in rat ovary were analyzed using real-time PCR and ELISA. In addition, we also analyzed the p38 and p-p38 protein expression in the ovary. Our results demonstrate that HO-1 is an anti-inflammatory factor in LPS-stimulated ovary, which regulates the inflammatory response through downregulation of p38 signaling pathways in rat ovary.
KEY WORDSheme oxygenase-1 LPS inflammation p38 ovary
This work has received funding from the Provincial Project for Agricultural Techniques (BE2014301) and the Natural Science Foundation of China (31372290).
- 1.AI-Owais, M.M., J.L. Scragg, M.L. Dallas, H.E. Boycott, P. Warburton, A. Chakrabarty, J.P. Boyle, and C. Peers. 2012. Carbon monoxide mediates the anti-apoptotic effects of heme oxygenase-1 in medulloblastoma DAOY cells via K+ channel inhibition. Journal of Biological Chemistry 287: 24754–24764.CrossRefGoogle Scholar
- 4.Drewa, G., E. Krzyzyńska-Malinowska, A. Woźniak, F. Protas-Drozd, C. MilaKierzenkowska, M. Rozwodowska, and R. Czajkowski. 2002. Activity of superoxide dismutase and catalase and the level of lipid peroxidation products reactive with TBA in patients with psoriasis. Medical Science Monitor 8: 338–343.Google Scholar
- 10.Jung, C.H., H. Jung, Y.C. Shin, J.H. Park, C.Y. Jun, H.M. Kim, H.S. Yim, M.G. Shin, H.S. Bae, S.H. Kim, and S.G. Ko. 2007. Eleutherococcus senticosus extract attenuates LPS-induced iNOS expression through the inhibition of Akt and JNK pathways in murine macrophages. Journal of Ethnopharmacology 113: 183–187.CrossRefPubMedGoogle Scholar
- 17.Park, E.J., Y.M. Kim, S.W. Park, H.J. Kim, J.H. Lee, D.U. Lee, and K.C. Chang. 2013. Induction of HO-1 through p38 MAPK/Nrf2 signaling pathway by ethanol extract of Inula helenium L. reduces inflammation in LPS-activated RAW 264.7 cells and CLP-induced septic mice. Food and Chemical Toxicology 55: 386–395.CrossRefPubMedGoogle Scholar
- 20.Shimizu, T., K. Miyauchi, K. Shirasuna, H. Bollwein, F. Magata, C. Murayama, and A. Miyamoto. 2012. Effects of lipopolysaccharide (LPS) and peptidoglycan (PGN) on estradiol production in bovine granulosa cells from small and large follicles. Toxicology In Vitro 26: 1134–1142.CrossRefPubMedGoogle Scholar
- 24.Welt, C., A. Falorni, A. Taylor, K. Martin, and J. Hall. 2005. Selective theca cell dysfunction in autoimmune oophoritis results in multifollicular development, decreased estradiol, and elevated inhibin B levels. Journal of Clinical Endocrinology and Metabolism 90: 3069–3076.CrossRefPubMedGoogle Scholar
- 27.Zenclussen, M.L., F. Jensen, S. Rebelo, T. El-Mousleh, P.A. Casalis, and A.C. Zenclussen. 2012. Heme oxygenase-1 expression in the ovary dictates a proper oocyte ovulation, fertilization, and corpora lutea maintenance. American Journal of Reproductive Immunology 67: 376–382.CrossRefPubMedGoogle Scholar
- 28.Zenclussen, M.L., F. Jensen, S. Rebelo, T. El-Mousleh, and A.C. Casalis PA. 2014. Hormonal fluctuations during the estrous cycle modulate heme oxygenase-1 expression in the uterus. Frontiers in Endocrinology (Lausanne) 5: 32.Google Scholar