Expression profile of chemokines and chemokine receptors in epithelial cell layers of oral lichen planus

Ichimura, Mana; Hiratsuka, Koichi; Ogura, Naomi; Utsunomiya, Tohru; Sakamaki, Hiroyuki; Kondoh, Toshirou; Abiko, Yoshimitsu; Otake, Shigeo; Yamamoto, Masafumi

doi:10.1111/j.1600-0714.2006.00402.x

Cited by 61 publications

(80 citation statements)

References 53 publications

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“…During inflammation, these keratinocyte receptors may contribute to CCR5-dependent autocrine and paracrine signaling pathways. For example, keratinocytes in inflammatory disorders such as oral lichen planus express RANTES/CCL5, a ligand specific for CCR5 (60), and a potential ligand in a CCR5-dependent autocrine loop. Inflammatory cells in inflamed gingiva also express the chemokines MCP-2, MIP-1␣, and MIP-1␤, which are also ligands for CCR5 (61) and suggestive of a potential paracrine CCR5-dependent pathway.…”

Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalisSelectively Up-Regulates the HIV-1 Coreceptor CCR5 in Oral Keratinocytes

Giacaman

Nobbs

Ross

et al. 2007

The Journal of Immunology

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Primary infection of oral epithelial cells by HIV-1, if it occurs, could promote systemic infection. Most primary systemic infections are associated with R5-type HIV-1 targeting the R5-specific coreceptor CCR5, which is not usually expressed on oral keratinocytes. Because coinfection with other microbes has been suggested to modulate cellular infection by HIV-1, we hypothesized that oral keratinocytes may up-regulate CCR5 in response to the oral endogenous pathogen Porphyromonas gingivalis by cysteine-protease (gingipains) activation of the protease-activated receptors (PARs) or LPS signaling through the TLRs. The OKF6/TERT-2-immortalized normal human oral keratinocyte line expressed CXCR4, whereas CCR5 was not detectable. When exposed to P. gingivalis ATCC 33277, TERT-2 cells induced greater time-dependent expression of CCR5-specific mRNA and surface coreceptors than CXCR4. By comparing arg- (Rgp) and lys-gingipain (Kgp) mutants, a mutant deficient in both proteases, and the action of trypsin, P. gingivalis Rgp was strongly suggested to cleave PAR-1 and PAR-2 to up-regulate CCR5. CCR5 was also slightly up-regulated by an isogenic gingipain-deficient mutant, suggesting the presence of a nongingipain-mediated mechanism. Purified P. gingivalis LPS also up-regulated CCR5. Blocking TLR2 and TLR4 receptors with Abs attenuated induction of CCR5, suggesting LPS signaling through TLRs. P. gingivalis, therefore, selectively up-regulated CCR5 by two independent signaling pathways, Rgp acting on PAR-1 and PAR-2, and LPS on TLR2 and TLR4. By inducing CCR5 expression, P. gingivalis coinfection could promote selective R5-type HIV-1 infection of oral keratinocytes.

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Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalisSelectively Up-Regulates the HIV-1 Coreceptor CCR5 in Oral Keratinocytes

Giacaman

Nobbs

Ross

et al. 2007

The Journal of Immunology

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“…These chemokines are produced and secreted by innate immune cells, such as macrophages, and exert their effect mainly on the adaptive immune system. It is known that epithelial cells can produce CCL18, CCL21, and CXCL9 (22)(23)(24). These chemokines are thought to have a critical role in tumor suppression.…”

Section: Discussionmentioning

confidence: 99%

Hedgehog Pathway Inhibitors Promote Adaptive Immune Responses in Basal Cell Carcinoma

Otsuka

Dreier

Cheng

et al. 2015

Clinical Cancer Research

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Purpose: Basal cell carcinomas (BCCs) are tumors ignored by immune surveillance. Activated Hedgehog (Hh) signaling within primary cilia is a key driver in the pathogenesis of BCCs. We examined immune alterations during treatment with systemic Hh inhibitors.Experimental Design: We investigated biopsies from patients with BCC before (23 patients) and after 4 weeks of treatment (5 patients) with Hh signaling inhibitor. Ber-Ep4, BCL-2, Ki-67, CD4, CD8, MHC class I, HLA-DR-class II, and SOX9 were analyzed by immunohistochemistry. Primary cilia were analyzed by double immunofluorescence of acetylated tubulin and SOX9. Differential gene expression for 84 cytokines and chemokines was analyzed in 3 patients.Results: After 4 weeks of treatment, we found reduction of Ki-67, SOX9, Ber-EP4, and BCL-2 expression in tumors associated with morphologic signs of squamous differentiation. In addition, the number of cilia-positive BCC cells was significantly decreased. An upregulation of MHC I expression on the cell membranes of residual tumor cells and an influx of CD4 þ , HLA-DR-class II þ, and CD8 þ cells with invasion into the tumor cell nests were found. Finally, qPCR arrays showed the differential expression of genes involved in modulating immune responses. Conclusions:We show that Hh pathway inhibitor-induced tumor regression is accompanied by a dynamic change of the microenvironment with a disruption of immune privilege involving an influx of cytotoxic T cells, activation of the adaptive immune functions, and a profound alteration of the local chemokine/cytokine network.

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“…Cytotoxic T-cell infiltration into the epithelium results in apoptotic basal keratinocytes. Theoretically, it may be induced by CXCR3 and CCR5 mediated signaling pathways initiated by both, T-cells and keratinocytes [9,10]. There have been no previously reported HLA studies in this variant of LP.…”

Section: Etiologymentioning

confidence: 99%

A Review of Vulvovaginal-Gingival Syndrome. Case Report

Grau¹,

Roig²,

Juncadella³

et al. 2017

UCMS

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Abstract:Vulvovaginal-gingival syndrome (VVGS) is a chronic mucocutaneous disease of unknown etiology, which consists of a triad of symptoms: vulvar, vaginal and gingival of lichen planus (LP) lesions. The evidence suggests an autoimmune response, a genetic and probably hormonal component. Associated factors observed in LP include stress/anxiety, hepatitis C virus (HCV) and autoimmune diseases, among others. The most serious complication of oral and possibly also vulvar Lichen Planus is the development of squamous cell carcinoma. Corticosteroids are the mainstay treatment for LP in order to control inflammatory activity. In case of failure, immunosuppressive agents can be used (Tacrolimus and Cyclosporine). We present an illustrated case of VVGS who over the years developed tongue cancer and, 10 years later, a vulvar cancer. Oral Lichen Planus (OLP) should be referred to the appropriate specialists to rule out involvement of other mucous membranes and track it early to diagnose a possible malignant transformation. The efficient management of VVGS involves a multidisciplinary approach involving gynecologists, dermatologists and stomatologists.

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Expression profile of chemokines and chemokine receptors in epithelial cell layers of oral lichen planus

Abstract: Infiltration of LCs is orchestrated by CCR6. Further, LCs residing in the lesional epithelia may be a mature phenotype. Moreover, infiltration of T cells in OLP could be mediated by signaling pathways through CXCR3 and CCR5.

Cited by 61 publications

References 53 publications

Porphyromonas gingivalisSelectively Up-Regulates the HIV-1 Coreceptor CCR5 in Oral Keratinocytes

Porphyromonas gingivalisSelectively Up-Regulates the HIV-1 Coreceptor CCR5 in Oral Keratinocytes

Hedgehog Pathway Inhibitors Promote Adaptive Immune Responses in Basal Cell Carcinoma

A Review of Vulvovaginal-Gingival Syndrome. Case Report

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