title: Reduced CX3CL1 Secretion Contributes to the Susceptibility of Oral Leukoplakia-Associated Fibroblasts toCandida albicans.
abstract: Candida leukoplakia (OLK) is a kind of oral leukoplakia combined with chronic candidal infection, which plays an important role in the malignant transformation of OLK. However, little is known about the etiology, including susceptibility of leukoplakia to candidal adhesion, invasion and infection. Some antimicrobial peptides secreted by oral epithelial cells or fibroblasts potentially have antifungal activities againstCandida albicans (C. albicans). In this study, we established three co-culture models to simulate differentC. albicans-fibroblasts interactions during progression of candida leukoplakia. The susceptibility of oral leukoplakia-associated fibroblasts (LKAFs) toC. albicansand its underlying mechanism were determined. Samples of 14 LKAFs and 10 normal fibroblasts (NFs) were collected. The co-culture models showed that LKAFs had promoted the adhesion, invasion, and survival ofC. albicanscompared with NFs. CX3CL1, a chemokine with antifungal activity, was less abundant in LKAFs than NFs. Overexpression of CX3CL1 via transfection in LKAFs could partly restore the resistance toC. albicans. We also showed that inhibition of ERK could suppress CX3CL1 secretion. While phosphor-ERK was inhibited in LKAFs compared with NFs. Besides, the mRNA expression of a shedding enzyme for CX3CL1, disintegrin and metalloproteinase domain (ADAM) 17 was decreased in LKAFs than NFs. In conclusion, LKAFs produced and secreted less CX3CL1 by inhibiting the ERK signaling pathway, thereby contributing to impaired cell resistance toC. albicans.
authors.affiliation: State Key Laboratory of Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University Chengdu, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Oral Diseases, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan UniversityChengdu, China; Department of Oral Medicine, School of Stomatology, Dalian Medical UniversityDalian, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oral Diseases, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University Chengdu, China.
authors.forename: Xueke
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University Chengdu, China.
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Oral Diseases, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University Chengdu, China.
authors.forename: Changlei
authors.initials: C
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University Chengdu, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University Chengdu, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oral Diseases, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University Chengdu, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhou
mesh_terms: D002176:Candida albicans / Q000502:physiology*; D002180:Candidiasis, Oral / Q000276:immunology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D018920:Coculture Techniques; D004198:Disease Susceptibility; D004705:Endocytosis; D005347:Fibroblasts / Q000382:microbiology*; D006801:Humans; D007972:Leukoplakia, Oral / Q000150:complications / Q000473:pathology*; D020935:MAP Kinase Signaling System; D008954:Models, Biological
chemical_list: C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1
keywords: CX3CL1; Candida albicans; antifungal peptide; co-culture models; fibroblast; leukoplakia