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HbAHP‐25 attenuates HIV‐1 gp120 mediated inflammation and barrier dysfunction
Author(s) -
Bashir T,
Reddy KVR
Publication year - 2018
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/hiv.12569
Subject(s) - tight junction , viability assay , blot , medicine , in vitro , inflammation , cytokine , microbiology and biotechnology , proinflammatory cytokine , cell culture , immunology , biology , biochemistry , gene , genetics
Objectives Development of Hb AHP ‐25, a peptide that prevents HIV ‐1 entry into cells by blocking gp120‐ CD 4 interaction, as a topical anti‐ HIV drug, necessitates that it is first tested for toxic or abrasive effects on genital epithelial cells and also on the vaginal microbiome. The present study was, therefore, undertaken to investigate whether: (1) Hb AHP ‐25 has any adverse effect on growth and membrane integrity of various cell lines, and (2) Hb AHP ‐25 neutralizes gp120 mediated insults on genital epithelial cells. Methods MTT and trans‐epithelial resistance ( TER ) assays were performed to assess the viability and integrity of epithelial cells. Real‐time PCR and Immunofluorescence/Western blotting were used to decipher the expression of tight junction proteins, at the mRNA and protein levels, respectively. A multiplex cytokine assay was performed to quantify the cytokines. Results Hb AHP ‐25 had no adverse effect on the viability of VK 2/E6E7, End1/E6E7, Ect1/E6E7 and HEC ‐1A cells, and also on growth of lactobacilli. The barrier integrity of Hb AHP ‐25‐treated cells remained unaltered. Expression of tight junction proteins, Claudin‐1 and ZO ‐1, at transcript and protein levels, remained unaltered in Hb AHP ‐25‐treated HEC ‐1A cells. Interestingly, Hb AHP ‐25 treatment prevented the breach of barrier integrity caused by gp120. Further, Hb AHP ‐25 did not elicit the expression of inflammatory cytokines. Instead, the in vitro induction of inflammatory cytokines by gp120 was also abrogated in the presence of Hb AHP ‐25. Conclusion Hb AHP ‐25 is exceedingly safe to genital epithelial cells and attenuates HIV ‐1 gp120‐mediated barrier dysfunction by limiting excessive inflammation. This study provides significant evidences in the favor of Hb AHP ‐25's potential as a topical anti‐ HIV agent.