Regulation of CXCL9/10/11 in Oral Keratinocytes and Fibroblasts

Ohta, Kouji; Shigeishi, Hideo; Taki, Masayuki; Nishi, Hiromi; Higashikawa, Koichiro; Takechi, Masaaki; Kamata, Nobuyuki

doi:10.1177/154405910808701211

Cited by 38 publications

(32 citation statements)

References 35 publications

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“…The T-cell–attracting chemokines CXCL9, 10, and 11 are known to be induced by IFNγ in various cell types, including ECs (Sauty et al , 1999; Kanda et al , 2007; Kanda and Watanabe, 2007; Ohta et al , 2008; Kawaguchi et al , 2009). Although CD40 stimulation salvaged the expression levels of CXCL9 , CXCL10 , and CXCL11 in HPV-positive ECs to similar levels found in noninfected ECs (Figure 4d–f), ELISA assays showed that hrHPV-positive ECs still secreted lower levels of CXCL9 and CXCL10 compared with noninfected ECs (Figure 4g and not shown).…”

Section: Resultsmentioning

confidence: 99%

CD40-Mediated Amplification of Local Immunity by Epithelial Cells Is Impaired by HPV

Tummers

Goedemans

Jha

et al. 2014

Journal of Investigative Dermatology

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The interaction between the transmembrane glycoprotein surface receptor CD40 expressed by skin epithelial cells (ECs) and its T-cell–expressed ligand CD154 was suggested to exacerbate inflammatory skin diseases. However, the full spectrum of CD40-mediated effects by ECs underlying this observation is unknown. Therefore, changes in gene expression after CD40 ligation of ECs were studied by microarrays. CD40-mediated activation for 2 hours stimulated the expression of a coordinated network of immune-involved genes strongly interconnected by IL8 and TNF, whereas after 24 hours anti-proliferative and anti-apoptotic genes were upregulated. CD40 ligation was associated with the production of chemokines and the attraction of lymphocytes and myeloid cells from peripheral blood mononuclear cells (PBMCs). Thus, CD40-mediated activation of ECs resulted in a highly coordinated response of genes required for the local development and sustainment of adaptive immune responses. The importance of this process was confirmed by a study on the effects of human papilloma virus (HPV) infection to the EC's response to CD40 ligation. HPV infection clearly attenuated the magnitude of the response to CD40 ligation and the EC's capacity to attract PBMCs. The fact that HPV attenuates CD40 signaling in ECs indicates the importance of the CD40-CD154 immune pathway in boosting cellular immunity within epithelia.

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Section: Resultsmentioning

confidence: 99%

CD40-Mediated Amplification of Local Immunity by Epithelial Cells Is Impaired by HPV

Tummers

Goedemans

Jha

et al. 2014

Journal of Investigative Dermatology

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“…CXCL9 is a T-cell chemoattractant (Gorbachev et al, 2007; Hertenstein et al, 2011), which is secreted by all kinds of cell types including neutrophils, monocytes, endothelial cells and fibroblasts (Taub et al, 1993). Studies have shown that in the setting of disease or stimulation with pre-inflammatory cytokines, the level of CXCL9 was increased (Coma et al, 2006; Ohta et al, 2008). C-X-C motif chemokine 13 (CXCL13), also known as B lymphocyte chemoattractant is a homeostatic chemokine that is constitutively expressed in secondary lymphoid tissue and involved in lymphoid organogenesis (Carlsen et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

CpG Oligodeoxynucleotides Induce Differential Cytokine and Chemokine Gene Expression Profiles in Dapulian and Landrace Pigs

Yang

Wang

et al. 2016

Front. Microbiol.

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Oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) mimic the immunostimulatory activity of microbial DNA by interacting with Toll-like receptor 9 (TLR9) to activate both the innate and adaptive immune responses in different species. However, few studies have been published to compare the effects of CpG ODN on different pig breeds. Therefore, in this study, whole blood gene expression profiles of DPL and Landrace pigs treated with CpG ODN were studied using RNA-seq technology. Five Hundred differentially expressed genes (DEGs) were identified between the two breeds. DPL pigs had significantly higher number of immune-relevant DEGs than the Landrace pigs after CpG ODN treatment. Pathway analysis showed that cytokine-cytokine receptor interaction and chemokine signaling pathway were the major enriched pathways of the immune-relevant DEGs. Further in vitro experiments showed that PBMCs of the DPL pigs had significantly higher levels of TLR9 mRNA than those of the Landrace pigs, both before and after CpG ODN stimulation. Cytokine and chemokine induction in the PBMCs of both breeds were also measured after CpG ODN stimulation. Our data showed that mRNA levels of cytokines (IFNα, IL8, IL12 p40) and chemokines (CXCL9, CXCL13) were significantly higher in the PBMCs of the DPL pigs than those of the Landrace pigs. Taken together, our data provide new information regarding the pig breed difference in response to CpG ODN stimulation and that higher levels of TLR9 mRNA in DPL pigs may be a major contributor for disease resistance.

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“…Primary cultures of human keratinocytes and fibroblasts from oral mucosal biopsy samples from healthy volunteers were prepared as previously described [8]. Informed consent for acquisition was obtained according to a protocol approved by the Ethical Committee of Hiroshima University.…”

Section: Methodsmentioning

confidence: 99%

“…We previously reported that oral keratinocytes and fibroblasts produce CXCL10, which is thought to attract immune cells to the site of oral inflammation [8]. The major function of CXCL10 in host defense against viral infection has been shown in CXCL10-/- mice, in which it impaired recruitment of effector T cells and NK cells to sites of infection/inflammation [9,10].…”

Section: Introductionmentioning

confidence: 99%

Expression and Function of RIG-I in Oral Keratinocytes and Fibroblasts

Ohta

Fukui

Shigeishi

et al. 2014

Cell Physiol Biochem

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Background: Innate immune response by oral mucosal cells may be the first line of host defense against viral infection. Retinoic acid-inducible gene-I (RIG-I) recognizes viral dsRNA in the cytoplasm, and RIG-I-mediated signaling regulates antiviral type I IFN, and inflammatory chemokine production. Here, we tested the hypothesis that oral mucosal cell participation in host defense against viral infection via RIG-I. Methods: RIG-I expression was detected in immortalized oral keratinocytes (RT7), oral fibroblasts (GT1) using and RT-PCR and immunohistochemistry. RT7 and GT1 were exposed to dsRNA virus mimic Poly I:C-LMW/LyoVec (PLV). Expression of IFN-β and CXCL10 via RIG-I was examined by Real-time RT-PCR and ELISA. Phosphorylation of IRF3 and STAT1 were detected by western blotting. Results: RT7 and GT1 constitutively expressed RIG-I in the cytoplasm. Furthermore, PLV increased IFN-β and CXCL10 productions in both RT7 and GT1 via RIG-I concurrent with phosphorylation of IRF3 and STAT1. PLV-induced CXCL10 production was attenuated by neutralization of IFN-β and blocking of IFN-α/β receptor (IFNAR), indicating primal IFN-β production via the RIG-I-IRF3 axis, which eventually induces CXCL10 production via the IFNAR -STAT1 axis. Conclusion: We propose that RIG-I in oral keratinocytes and fibroblasts may cumulatively develop host-defense mechanisms against viral infection in oral mucosa.

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Regulation of CXCL9/10/11 in Oral Keratinocytes and Fibroblasts

Cited by 38 publications

References 35 publications

CD40-Mediated Amplification of Local Immunity by Epithelial Cells Is Impaired by HPV

CD40-Mediated Amplification of Local Immunity by Epithelial Cells Is Impaired by HPV

CpG Oligodeoxynucleotides Induce Differential Cytokine and Chemokine Gene Expression Profiles in Dapulian and Landrace Pigs

Expression and Function of RIG-I in Oral Keratinocytes and Fibroblasts

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