Inhibition of COX-2/PGE2 pathway mediates the protection of hydrogen sulfide against chemical hypoxiainduced injury to human skin keratinocytes

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YANG Chun-tao(Department of Physiology, Guangzhou Medical College, Guangzhou 510182, China)
DONG Qi(Department of Physiology, Guangzhou Medical College, Guangzhou 510182, China)
HAN Yan-fang()
GUO Run-min()
HU Fen()
Feng Jian-qiang()
MO Li-qiu(Department of Anesthesia, Huangpu Division of the First Affiliated Hospital, Sun Yat-sun University, Guangzhou 510070, China.)
Journal Title:
Chinese Journal of Biomedical Engineering
Volume 18, Issue 03, 2012
Key Word:
Hydrogen sulfide;Keratinocyte;Cyclooxygenase-2;Prostaglandin E2

Abstract: Objective To investigate the role of COX- 2/PGE2 pathway in protective effects of hydrogen sulfide against chemical hypoxia-induced injury to human skin keratinocytes (HaCaT cells).Methods The hypoxia-mimicking agent CoCl2 was used to process HaCaT cells and establish an in vitro model of hypoxia-induced skin injury.Before the exposure to CoCl2,HaCaT cells were pretreated with NaHs (a donor of H2S) for 30 mins.The impact of H2S on CoCl2-induced cell injury was then detected.The cell survival rate was determined by cell counting kit (CCK)- 8,the expression level of PGE2 in culture medium by enzyme-linked immunosorbcnt assay (ELISA) and the expression levels of COX-1 and COX-2 protein by Western blot assay.Results The 24 h treatment of HaCaT cells with 500 μmol/L CoCl2 could significantly lower the cell survival rate[ (56.3±5.4)%],promote the release of PGE2[ (395.7±65.0)%] and up-regulate the expression of COX-2 (all P<0.01).However,the treatment using CoCl2 did not obviously affect the expressions of COX - 1 in HaCaT cells (P>0.05).The pretreatment with NaHs (ranging from 200 to 400 μmol/L) could significantly inhibit the lowered cell survival,increascd rclcase of PGE2 and up-regulated expression of COX-2 caused by CoCl2.Additionally,NS-398,a selective inhibitor of COX-2,could also inhibit CoCl2-induced decrease in cell survival rate.Conclusions H2S can antagonize the chemical hypoxiainduced injury and protect HaCaT cells.Furthermore,this mechanism is associated with the inhibition of COX-2/PGE2 pathway.

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