![]() ![]() Innate immune recognition of viral infection triggers antiviral immune responses. However, none of the clinical, lifestyle, gynecological and treatment regime characteristics was predictive of persistent HPV infection in lupus patients. Although the majority of the otherwise healthy individuals clear HPV infection with time, almost half (48.5%) of the newly acquired HPV infections persisted for at least six months in lupus patients. Independent risk factors associated with the development of squamous intraepithelial lesion (SIL) in lupus patients included persistent oncogenic HPV infection and the use of cyclophosphamide. Previous studies have revealed an increase in the prevalence of abnormal Papanicolaou (Pap) smears among patients with systemic lupus erythematosus (SLE). Persistent infection with an oncogenic human papillomavirus (HPV)16 or 18 is thought to be necessary for the development of invasive cervical cancer, particularly among immunocompromised patients. ![]() Furthermore, reduction of nucleic acid-sensing TLRs 7, 8 and 9 in carcinogenic HPVs ensures that the expression of inducible pro-inflammatory cytokines is minimized to prevent the expression of antiviral ISGs (ISG15 and Mx-1) on a biologically relevant antiviral response. ![]() ![]() Upon infection, HPV further down-regulate TLR7 and 9 levels for viral persistence. In conclusion, prednisolone and TLR antagonist (hydroxychloroquine) may down-regulate protein levels of TLR7 and TLR9 in lupus patients, thereby decreasing the innate immune response against HPV infection. Functional data showed that the induction of pro-inflammatory cytokines by TLR ligands (R837, ssRNA and ODN2395) was greatly impaired in CaSki and HeLa than C33A cells. In cervical cell lines, TLRs 3, 7, 8, 9 protein levels and antiviral ISG15 and Mx-1 gene expressions were inhibited in two oncogenic HPV types. Independent explanatory variables associated with down-regulation of TLR7 level included HPV infection and a higher cumulative dose of prednisolone while a higher cumulative dose of hydroxychloroquine and HPV infection were associated with down-regulation of TLR9 level. For SLE with and without HPV infection, TLR7 and 9 levels were significantly lower in infected SLE than those in HPV-negative patients. Significantly decreased TLRs 7, 8 and 9 levels were observed in HPV-negative SLE compared to healthy controls. Resultsįor subjects with HPV infection, levels of TLR3 and TLR7 were significantly lower in lupus patients compared with controls. Ex vivo productions of cytokines and interferon-gamma (IFN-γ) upon TLR ligands stimulations were subsequently measured using cytometric bead array and ELISA. The effect and interferon-stimulated genes (ISGs) (ISG15 and Mx-1) gene expressions were then measured in oncogenic HeLa (HPV18), CaSki (HPV) and C33A (HPV negative) cell lines using flow cytometry and quantitative real-time PCR. Characteristics associated with the differential expression of TLRs in systemic lupus erythematosus (SLE) were elucidated. Protein levels of TLRs 3, 7, 8 and 9 in cervical epithelial cells of lupus patients and controls with or without HPV infection were assessed using flow cytometry. This study evaluated whether abnormal host innate immune response in lupus patients may enhance HPV persistence. The nucleic acid-specific Toll-like receptors (TLRs) locate at the endolysosomal compartments and trigger the induction of cytokines for the innate immune response. Prevalence of an abnormal Papanicolaou smear was significantly increased in lupus patients in cross-sectional studies, associated with a higher prevalence of high-risk human papillomavirus (HPV) infection. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |