Document Detail


L-selectin and P-selectin are novel biomarkers of cervicovaginal inflammation for preclinical mucosal safety assessment of anti-HIV-1 microbicide.
MedLine Citation:
PMID:  22391529     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Maohua Zhong; Benxia He; Jingyi Yang; Rong Bao; Yan Zhang; Dihan Zhou; Yaoqing Chen; Liangzhu Li; Chen Han; Yi Yang; Ying Sun; Yuan Cao; Yaoming Li; Wei Shi; Shibo Jiang; Xiaoyan Zhang; Huimin Yan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-05
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  56     ISSN:  1098-6596     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-14     Completed Date:  2012-09-13     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3121-32     Citation Subset:  IM    
Affiliation:
Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
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MeSH Terms
Descriptor/Qualifier:
Adenine / adverse effects,  analogs & derivatives
Animals
Anti-Infective Agents / adverse effects*
Benzalkonium Compounds / adverse effects
Biological Markers / metabolism*
Carboxymethylcellulose Sodium / adverse effects
Cervix Uteri / drug effects,  metabolism
Chemokine CCL2
Female
HIV Infections / drug therapy
Inflammation / chemically induced*,  metabolism*
Interleukin-6 / metabolism
L-Selectin / metabolism*
Mice
Mice, Inbred C57BL
Mucous Membrane / drug effects
Nonoxynol / adverse effects,  therapeutic use
Organophosphonates / adverse effects
P-Selectin / metabolism*
Sodium Dodecyl Sulfate / adverse effects
Chemical
Reg. No./Substance:
0/Anti-Infective Agents; 0/Benzalkonium Compounds; 0/Biological Markers; 0/Chemokine CCL2; 0/Interleukin-6; 0/Organophosphonates; 0/P-Selectin; 107021-12-5/tenofovir; 126880-86-2/L-Selectin; 151-21-3/Sodium Dodecyl Sulfate; 26027-38-3/Nonoxynol; 73-24-5/Adenine; 9004-32-4/Carboxymethylcellulose Sodium
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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