title: L-selectin and P-selectin are novel biomarkers of cervicovaginal inflammation for preclinical mucosal safety assessment of anti-HIV-1 microbicide.
abstract: 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.
authors.affiliation: Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Maohua
authors.initials: M
authors.lastname: Zhong
authors.forename: Benxia
authors.initials: B
authors.lastname: He
authors.forename: Jingyi
authors.initials: J
authors.lastname: Yang
authors.forename: Rong
authors.initials: R
authors.lastname: Bao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dihan
authors.initials: D
authors.lastname: Zhou
authors.forename: Yaoqing
authors.initials: Y
authors.lastname: Chen
authors.forename: Liangzhu
authors.initials: L
authors.lastname: Li
authors.forename: Chen
authors.initials: C
authors.lastname: Han
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cao
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Huimin
authors.initials: H
authors.lastname: Yan
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives; D000818:Animals; D000890:Anti-Infective Agents / Q000009:adverse effects*; D001548:Benzalkonium Compounds / Q000009:adverse effects; D015415:Biomarkers / Q000378:metabolism*; D002266:Carboxymethylcellulose Sodium / Q000009:adverse effects; D002584:Cervix Uteri / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000187:drug effects; D017137:Nonoxynol / Q000009:adverse effects / Q000627:therapeutic use; D063065:Organophosphonates / Q000009:adverse effects; D019007:P-Selectin / Q000378:metabolism*; D012967:Sodium Dodecyl Sulfate / Q000009:adverse effects; D000068698:Tenofovir
chemical_list: D000890:Anti-Infective Agents; D001548:Benzalkonium Compounds; D015415:Biomarkers; D018932:Chemokine CCL2; D015850:Interleukin-6; D063065:Organophosphonates; D019007:P-Selectin; D019041:L-Selectin; D017137:Nonoxynol; D012967:Sodium Dodecyl Sulfate; D000068698:Tenofovir; D000225:Adenine; D002266:Carboxymethylcellulose Sodium