Regulation of Inflammatory Pathways in Cancer and Infectious Disease of the Cervix

Adefuye, Anthonio Oladele; Sales, Kurt J.

doi:10.6064/2012/548150

Cited by 24 publications

(27 citation statements)

References 80 publications

(101 reference statements)

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“…COX-2 is an enzyme with an imperative role in the metabolism of arachidonic acid, which leads to the production of prostaglandins, which in turn promote inflammation [32]. In fact, COX-2 is over-expressed in several malignancies, including cervical cancer [33][34][35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Celecoxib promotes degranulation of CD8+ T cells in HPV-induced lesions of K14-HPV16 transgenic mice

et al. 2016

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Aims: Human papillomavirus (HPV) is a known biologic carcinogen which is commonly transmitted through sexual intercourse. CD8 + T cells are known effectors against tumour cells and an important prognostic marker in HPV-induced cancers. COX-2 inhibitors enhance CD8 + T cell activity against some cancers. In this work, we sought to study the presence and activation of CD8 + T lymphocytes in lesions from K14-HPV16 transgenic mice and the immunomodulatory effect of celecoxib (CXB) over these cells.Main methods: Skin samples of CXB-treated and untreated HPV16 -/-and HPV16 +/-mice were enzymatically digested and analysed by flow cytometry to assess CD8 + and CD8 + CD107a + T cell infiltrates. Matched skin samples were classified histologically.Key findings: HPV16 +/-mice presented higher CD8 + T cell infiltration than HPV16 -/-animals (P 0.001). Older HPV16 +/-animals showed epidermal dysplasia and increased percentages of CD8 + CD107a + T cells compared with younger animals with hyperplasia (P 0.001), validating this model for testing the effects of celecoxib on CD8 + T cells. CXB-treated HPV16 +/-mice showed higher percentages of CD8 + CD107a + T cells compared with untreated HPV16 +/-animals (P 0.01), but no differences were observed concerning the progression of epidermal lesions.Significance: These findings indicate that celecoxib enhances the degranulation of CD8 + T cells on HPV16-induced lesions, suggesting the potential clinical use of COX-2 inhibitors. Additionally, this study demonstrates the usefulness of the K14-HPV16 mouse model for testing therapeutic immunomodulatory approaches.

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Section: Discussionmentioning

confidence: 99%

Celecoxib promotes degranulation of CD8+ T cells in HPV-induced lesions of K14-HPV16 transgenic mice

et al. 2016

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“…Of all HPV positive women, approximately 15% develop a persistent infection of the cervical epithelium [76]. Persistent HPV infections may slowly progress to cervical low-and highgrade squamous intraepithelial lesions (LSIL, HSIL) with the potential to develop to invasive squamous cell carcinoma (SCC) [77], Figure 5.…”

Section: Cervical Hpv Lesionsmentioning

confidence: 99%

“…Persistent HPV infections may slowly progress to cervical low-and highgrade squamous intraepithelial lesions (LSIL, HSIL) with the potential to develop to invasive squamous cell carcinoma (SCC) [77], Figure 5. Cofactors increasing the risk of progression are a compromised immune system and other co-infections such as HSV 2, Chlamydia trachomatis, Neisseria gonorrhoeae and BV [76,78,79]. Prolonged use of oral contraceptives (OC), high parity and smoking are other risk factors for persistent infection [80].…”

Section: Cervical Hpv Lesionsmentioning

confidence: 99%

Expression of Psoriasin in Human Papillomavirus–Induced Cervical High-Grade Squamous Intraepithelial Lesions

Alvendal

Kamolvit

Wagner

et al. 2019

J Low Genit Tract Dis

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Background: Infections of the female genital tract are common and have severe impact on the quality of life and sexual health of affected women. The innate immune system is crucial and is involved in the defense of infections. Understanding innate immunity of the vaginal and cervical mucosa is important to enable development of future preventive and therapeutic strategies for genital infections. Objective: The aim of this thesis was to investigate innate immune factors in women with recurrent candida vulvovaginitis (RVVC) and high grade squamous intraepithelial lesions (HSIL) of the cervix, induced by human papilloma virus (HPV). This in order to contribute to the understanding of the innate immune response in these two common infections of the lower female genital tract. Material and Methods: Clinical examinations, measurements of intravaginal nitric oxide (NO) levels and vaginal biopsies were performed in 28 patients with RVVC and 31 healthy controls. Cervical biopsies and vaginal lavage were collected from 19 patients with HPV induced HSIL and 14 controls. Immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA), western blot and reverse transcriptase real time polymerase chain reaction (PCR)) were used to identify and quantify inducible nitric oxide synthase (iNOS), antimicrobial proteins, cytokines and encoding genes. Adhesion and binding assays were performed to evaluate the adhesive capacity of candida and to demonstrate the binding between candida and the antimicrobial protein psoriasin. Transmission electron microscopy was conducted to measure the cell wall thickness in C. albicans affected by psoriasin. To evaluate a new treatment strategy for RVVC, the effect of chlorhexidine digluconate and fluconazole on C. albicans eradication and biofilm was investigated in RVVC and commensal strains, using the crystal violet method and viable count. Results: NO levels were significantly higher in patients during acute infection compared to controls. Levels decreased after fluconazole treatment but remained higher than in controls. Furthermore, increased expression of iNOS was observed in the epithelial basal layer in patients both before and after treatment. There were positive correlations between NO levels, clinical symptoms and examination scores. Findings indicated that C. albicans induces production of psoriasin during mucosal candida infection. Psoriasin was shown to interact with β-glucan in the candida cell wall and inhibit candida adhesion to surfaces. In HPV induced HSIL, psoriasin expression and protein levels increased significantly after surgical treatment and reached similar levels as in controls. The mRNA expression of the proinflammatory cytokine IL-8 was higher before treatment and restored to the same levels as in controls six months after lesions were excised. Chlorhexidine digluconate prevented new biofilm formation and reduced already established C. albicans biofilm. Moreover, the number of candida cells in both planktonic state and within the biofilm were significantly decreased....

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“…It has been shown that persistent infection with high-risk HPVs leads to an increase in pro-inflammatory cytokines, including IL-6, TNF-α and MIP-1α [13]. In addition, high-risk HPV type 16 (HPV16) is able to increase the expression of cyclooxygenase-2 (COX-2), a key enzyme in the synthesis of prostaglandins, which are important mediators of inflammation [14,15]. Until now, only a single study has reported HPV DNA sequences in CSOM, whereby different HPV genotypes, including HPV16, HPV18 and HPV6, have been detected in 30.7% of CSOM [4].COMC is a form of expanding growth consisting of keratinizing squamous cell epithelium [16].…”

mentioning

confidence: 99%

High Human Papillomavirus DNA loads in Inflammatory Middle Ear Diseases

et al. 2020

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Background. Previous studies reported human papillomaviruses (HPVs) in middle ear tumors, whereas these viruses have been poorly investigated in chronic inflammatory middle ear diseases. We investigated HPVs in non-tumor middle ear diseases, including chronic otitis media (COM). Methods. COM specimens (n = 52), including chronic suppurative otitis media (CSOM) (n =38) and cholesteatoma (COMC) (n = 14), as well as normal middle ear (NME) specimens (n = 56) were analyzed. HPV sequences and DNA loads were analyzed by quantitative-PCR. HPV genotyping was performed by direct sequencing. Results. HPV DNA was detected in 23% (12/52) of COM and in 30.4% (17/56) of NME (p > 0.05). Specifically, HPV DNA sequences were found in 26.3% (10/38) of CSOM and in 14.3% (2/14) of COMC (p > 0.05). Interestingly, the HPV DNA load was higher in COMC (mean 7.47 copy/cell) than in CSOM (mean 1.02 copy/cell) and NME (mean 1.18 copy/cell) (P = 0.03 and P = 0.017 versus CSOM and NME, respectively). HPV16 and HPV18 were the main genotypes detected in COMC, CSOM and NME. Conclusions. These data suggest that HPV may infect the middle ear mucosa, whereas HPV-positive COMCs are associated with higher viral DNA loads as compared to NME.Pathogens 2020, 9, 224 2 of 10 mucosa sampled from CSOM patients [11]. However, the etiology of CSOM remains to be determined. The relationship between HPV infection and inflammation has been previously reported [12]. It has been shown that persistent infection with high-risk HPVs leads to an increase in pro-inflammatory cytokines, including IL-6, TNF-α and MIP-1α [13]. In addition, high-risk HPV type 16 (HPV16) is able to increase the expression of cyclooxygenase-2 (COX-2), a key enzyme in the synthesis of prostaglandins, which are important mediators of inflammation [14,15]. Until now, only a single study has reported HPV DNA sequences in CSOM, whereby different HPV genotypes, including HPV16, HPV18 and HPV6, have been detected in 30.7% of CSOM [4].COMC is a form of expanding growth consisting of keratinizing squamous cell epithelium [16]. There is great interest in the etiopathogenesis of HPV-associated cholesteatoma because HPV commonly infects the stratified epithelium [17,18]. However, conflicting data have been reported for HPV in COMC [10,[19][20][21]. HPV sequences have been detected in COMC with different prevalence, ranging from 3% to 70% [10,[19][20][21]. Moreover, no specific HPV genotypes have been associated with COMC, as high-and low-risk HPVs, such as HPV16, HPV18 and HPV6 and HPV11, have been detected [10,[19][20][21].There is emerging evidence that HPV infection can occur in different anatomical sites. Since HPV infects epithelia [22], all anatomical sites covered with epithelial tissue are potentially exposed to HPV infection. Apart from pluristratified tissues of the cervix [23], vulva [24] and oral pharynx [25], HPV sequences have been detected in simple epithelia from several anatomical sites such as lung [26], upper respiratory tract [27], larynx [28] and nose [29]. Since the middle ear muc...

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Regulation of Inflammatory Pathways in Cancer and Infectious Disease of the Cervix

Cited by 24 publications

References 80 publications

Celecoxib promotes degranulation of CD8+ T cells in HPV-induced lesions of K14-HPV16 transgenic mice

Celecoxib promotes degranulation of CD8+ T cells in HPV-induced lesions of K14-HPV16 transgenic mice

Expression of Psoriasin in Human Papillomavirus–Induced Cervical High-Grade Squamous Intraepithelial Lesions

High Human Papillomavirus DNA loads in Inflammatory Middle Ear Diseases

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