Immunohistochemical Localization of RNase 7 in Normal and Inflamed Oral Epithelia and Salivary Glands

Neopane, Puja; Paudel, Durga; Yoshida, Koki; Adhikari, Bhoj Raj; Morikawa, Tetsuro; Onishi, Aya; Hiraki, Daichi; Uehara, Osamu; Sato, Jun; Nishimura, Michiko; Chiba, Itsuo; Abiko, Yoshihiro

doi:10.1267/ahc.18027

Cited by 4 publications

(3 citation statements)

References 27 publications

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“…Although RNase 7 was localized mainly in the keratinized surface layers of the normal oral epithelium, it was often observed in the basaloid and spinous-like cells and the keratinized pearls of the OSCC tissues. As reported previously in normal and inflamed oral epithelium, the expression of RNase 7 was linked to keratinocyte differentiation in the current study (17). The increased expression of RNase 7 in the keratinized pearl may be due to the differentiation of the cells.…”

Section: Discussionsupporting

confidence: 88%

Involvement of RNase 7 in the malignant potential of oral squamous cell carcinoma cells

et al. 2020

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RNase 7 is involved in the innate immunity of the oral epithelium. Variations in the expression levels of RNase 7 have been reported in cutaneous squamous cell carcinoma, but not in oral squamous cell carcinoma (OSCC). The present study investigated the expression levels of RNase 7 in OSCC and its role in the malignant potential of these cells. The localization of RNase 7 in OSCC tissue sections was determined via immunohistochemistry. Positive staining for RNase 7 was observed around the epithelial pearls and spinous cells of the OSCC tissues. Four different types of OSCC cell lines (OSC-19, BSC-OF, SAS, and HSC-2) and a normal keratinocyte (HaCaT) were used. The mRNA and protein expression levels of RNase 7 were significantly higher in the OSCC cells compared to the HaCaT cells. Based on our hypothesis that high levels of RNase 7 expression may be involved in the malignant potential of OSCC cells, the effect of RNase 7 knockdown on both proliferation and invasion were evaluated by transfecting the cells with siRNA. Cell numbers, cell invasion, and MMP 9 expression levels were significantly higher in the siRNA-BSC-OF, -SAS, and -HSC-2 cells compared to the BSC-OF, SAS, and HSC-2 cells. The extent of differentiation of the siRNA-OSCC cells was examined using the differentiation and undifferentiation markers involucrin (INV) and K14, respectively. The expression level of K14 was significantly higher in the siRNA-OSCC cells compared to the OSCC cells. Alternatively, HSC-2 and SAS cells demonstrated higher expression levels of INV compared to the siRNA-HSC-2 and -SAS cells. These findings indicate that RNase 7 may contribute to the suppression of the malignant potential of OSCC.

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Section: Discussionsupporting

confidence: 88%

Involvement of RNase 7 in the malignant potential of oral squamous cell carcinoma cells

et al. 2020

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“…RNase1 is released from vascular endothelial cells at sites of acute inflammation ( 31 ). The salivary gland epithelium of SS forms an important niche for antigen-driven affinity maturation and persistence of anti-Ro60 and anti-La antibodies ( 32 , 33 ), and RNase7 production was shown to be enhanced in salivary glands with lymphocytic infiltrates in SS ( 34 ). RNase T2 is upregulated in response to tissue injury and functions as an intracellular and extracellular RNase ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

Positive and negative regulation of the Fcγ receptor–stimulating activity of RNA-containing immune complexes by RNase

Naito¹,

Ohmura²,

Higuchi³

et al. 2023

JCI Insight

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The U1RNP complex, Ro/SSA, and La/SSB are major RNA-containing autoantigens. Immune complexes (ICs) composed of RNA-containing autoantigens and autoantibodies are suspected to be involved in the pathogenesis of some systemic autoimmune diseases. Therefore, RNase treatment, which degrades RNA in ICs, has been tested in clinical trials as a potential therapeutic agent. However, no studies to our knowledge have specifically evaluated the effect of RNase treatment on the Fcγ receptor–stimulating (FcγR-stimulating) activity of RNA-containing ICs. In this study, using a reporter system that specifically detects FcγR-stimulating capacity, we investigated the effect of RNase treatment on the FcγR-stimulating activity of RNA-containing ICs composed of autoantigens and autoantibodies from patients with systemic autoimmune diseases such as systemic lupus erythematosus. We found that RNase enhanced the FcγR-stimulating activity of Ro/SSA- and La/SSB-containing ICs, but attenuated that of the U1RNP complex–containing ICs. RNase decreased autoantibody binding to the U1RNP complex, but increased autoantibody binding to Ro/SSA and La/SSB. Our results suggest that RNase enhances FcγR activation by promoting the formation of ICs containing Ro/SSA or La/SSB. Our study provides insights into the pathophysiology of autoimmune diseases involving anti-Ro/SSA and anti-La/SSB autoantibodies, and into the therapeutic application of RNase treatment for systemic autoimmune diseases.

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“…Ribonuclease 7 (RNase 7) is a ribonuclease that belongs to the RNase A superfamily. It is abundantly expressed in keratinocytes [ 157 ] and has also been described in oral epithelial cells [ 158 , 159 ]. Functional in vitro assays showed that RNase 7 in a mixture with self-deoxyribonucleic acid (DNA) was a strong trigger of IFN-α production by human DC through TLR-9 stimulation [ 160 ] and a potent repressor of Th2 cytokines production (IL-4, IL-13 and IL-5) by activated Th2 cells and CD4+ T cells [ 161 ].…”

Section: Cytoplasmic Alarmins In Ssmentioning

confidence: 99%

The Involvement of Alarmins in the Pathogenesis of Sjögren’s Syndrome

Sarrand

Baglione

Parisis

et al. 2022

IJMS

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Sjogren’s syndrome (SS) is a chronic autoimmune disease that affects exocrine glands, primarily the salivary and lachrymal glands. It is characterized by lymphoplasmacytic infiltration of the glandular tissues, ultimately leading to their dysfunction and destruction. Besides classic dry eyes and dry mouth defined as sicca syndrome, patients affected by the disease also typically display symptoms such as fatigue, pain and in more than 50% of cases, systemic manifestations such as arthritis, interstitial lung involvement, neurological involvement and an increased risk of lymphoma. The pathophysiological mechanisms underlying SS still remain elusive. The crucial role of innate immunity has been advocated in recent years regarding the pathogenesis of pSS, especially in the initiation and progression toward autoimmunity. Alarmins are endogenous molecules that belong to the large family of damage associated molecular pattern (DAMP). Alarmins are rapidly released, ensuing cell injury and interacting with pattern recognition receptors (PRR) such as toll-like receptors (TLR) to recruit and activate cells of the innate immune system and to promote adaptive immunity responses. This review highlights the current knowledge of various alarmins and their role in the pathogenesis of pSS.

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Immunohistochemical Localization of RNase 7 in Normal and Inflamed Oral Epithelia and Salivary Glands

Cited by 4 publications

References 27 publications

Involvement of RNase 7 in the malignant potential of oral squamous cell carcinoma cells

Involvement of RNase 7 in the malignant potential of oral squamous cell carcinoma cells

Positive and negative regulation of the Fcγ receptor–stimulating activity of RNA-containing immune complexes by RNase

The Involvement of Alarmins in the Pathogenesis of Sjögren’s Syndrome

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