PMID- 22391529 OWN - NLM STAT- MEDLINE DCOM- 20120913 LR - 20211021 IS - 1098-6596 (Electronic) IS - 0066-4804 (Print) IS - 0066-4804 (Linking) VI - 56 IP - 6 DP - 2012 Jun TI - L-selectin and P-selectin are novel biomarkers of cervicovaginal inflammation for preclinical mucosal safety assessment of anti-HIV-1 microbicide. PG - 3121-32 LID - 10.1128/AAC.05950-11 [doi] AB - A major obstacle thwarting preclinical development of microbicides is the lack of a validated biomarker of cervicovaginal inflammation. Therefore, the present study aims to identify novel noninvasive soluble markers in a murine model for assessment of microbicide mucosal safety. By performing cytokine antibody array analysis, we identified two adhesion molecules, L-selectin and P-selectin, which significantly increased when mucosal inflammation was triggered by nonoxynol-9 (N9), an anti-HIV-1 microbicide candidate that failed clinical trials, in a refined murine model of agent-induced cervicovaginal inflammation. We found that patterns of detection of L-selectin and P-selectin were obviously different from those of the two previously defined biomarkers of cervicovaginal inflammation, monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6). The levels of these two soluble selectins correlated better than those of MCP-1 and IL-6 with the duration and severity of mucosal inflammation triggered by N9 and two approved proinflammatory compounds, benzalkonium chloride (BZK) and sodium dodecyl sulfate (SDS), but not by two nonproinflammatory compounds, carboxymethyl celluose (CMC; microbicide excipients) and tenofovir (TFV; microbicide candidate). These data indicated that L-selectin and P-selectin can serve as additional novel cervicovaginal inflammation biomarkers for preclinical mucosal safety evaluation of candidate microbicides for the prevention of infection with HIV and other sexually transmitted pathogens. FAU - Zhong, Maohua AU - Zhong M AD - Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. FAU - He, Benxia AU - He B FAU - Yang, Jingyi AU - Yang J FAU - Bao, Rong AU - Bao R FAU - Zhang, Yan AU - Zhang Y FAU - Zhou, Dihan AU - Zhou D FAU - Chen, Yaoqing AU - Chen Y FAU - Li, Liangzhu AU - Li L FAU - Han, Chen AU - Han C FAU - Yang, Yi AU - Yang Y FAU - Sun, Ying AU - Sun Y FAU - Cao, Yuan AU - Cao Y FAU - Li, Yaoming AU - Li Y FAU - Shi, Wei AU - Shi W FAU - Jiang, Shibo AU - Jiang S FAU - Zhang, Xiaoyan AU - Zhang X FAU - Yan, Huimin AU - Yan H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120305 PL - United States TA - Antimicrob Agents Chemother JT - Antimicrobial agents and chemotherapy JID - 0315061 RN - 0 (Anti-Infective Agents) RN - 0 (Benzalkonium Compounds) RN - 0 (Biomarkers) RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-6) RN - 0 (Organophosphonates) RN - 0 (P-Selectin) RN - 126880-86-2 (L-Selectin) RN - 26027-38-3 (Nonoxynol) RN - 368GB5141J (Sodium Dodecyl Sulfate) RN - 99YXE507IL (Tenofovir) RN - JAC85A2161 (Adenine) RN - K679OBS311 (Carboxymethylcellulose Sodium) SB - IM MH - Adenine/adverse effects/analogs & derivatives MH - Animals MH - Anti-Infective Agents/*adverse effects MH - Benzalkonium Compounds/adverse effects MH - Biomarkers/*metabolism MH - Carboxymethylcellulose Sodium/adverse effects MH - Cervix Uteri/drug effects/metabolism MH - Chemokine CCL2 MH - Female MH - HIV Infections/drug therapy MH - Inflammation/*chemically induced/*metabolism MH - Interleukin-6/metabolism MH - L-Selectin/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mucous Membrane/drug effects MH - Nonoxynol/adverse effects/therapeutic use MH - Organophosphonates/adverse effects MH - P-Selectin/*metabolism MH - Sodium Dodecyl Sulfate/adverse effects MH - Tenofovir PMC - PMC3370781 EDAT- 2012/03/07 06:00 MHDA- 2012/09/14 06:00 PMCR- 2012/12/01 CRDT- 2012/03/07 06:00 PHST- 2012/03/07 06:00 [entrez] PHST- 2012/03/07 06:00 [pubmed] PHST- 2012/09/14 06:00 [medline] PHST- 2012/12/01 00:00 [pmc-release] AID - AAC.05950-11 [pii] AID - 05950-11 [pii] AID - 10.1128/AAC.05950-11 [doi] PST - ppublish SO - Antimicrob Agents Chemother. 2012 Jun;56(6):3121-32. doi: 10.1128/AAC.05950-11. Epub 2012 Mar 5.