Roopa Yadahalli1, Gargi S Sarode1, Sachin C Sarode1, Zafar Ali Khan2, Nishant Vyas3, Avinash H Kharat4, Shilpa Bhandi5, Kamran Habib Awan6, Shankargouda Patil7. 1. Department of Oral Pathology and Microbiology, Dr. D.Y.Patil Dental College and Hospital, Dr.D.Y.Patil Vidyapeeth, Pune, Maharashtra, India. 2. Department of Oral and Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Jouf University, Sakaka, Saudi Arabia. 3. Logical life science Pvt. Ltd, Pune, India. 4. Regenerative medicine laboratory, Dr. D.Y.Patil Dental College and Hospital, Dr.D.Y.Patil Vidyapeeth, Pune, India. 5. Department of Restorative Dental Science, Division of Operative Dentistry, College of Dentistry, Jazan University, Jazan 45142, Saudi Arabia. 6. College of Dental Medicine, Roseman University of Health Sciences, South Jordan, UT, United States. 7. Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan, Kingdom of Saudi Arabia. Electronic address: dr.ravipatil@gmail.com.
Abstract
BACKGROUND: Oral submucous fibrosis (OSMF) is a chronic disease with significantly increasing malignant transformation rate. To date the pathogenesis of OSMF has been considered to be associated with areca nut constituents and their action on fibroblasts. However, fibrosis is also associated with immunological factors such as chemokines. In-depth analysis of such factors is the need of the hour in OSMF to better understand the pathogenesis so that effective therapeutic strategies can be developed in the future. MATERIALS AND METHOD: Clinically diagnosed cases of OSMF (n=21) and healthy individuals (n=10) were enrolled in the present study. Chemokines such as CCL2, CCL3, CCL4, CCL5, CCL11, CCL17, CCL28, CXCL1, CXCL5, CXCL8, CXCL9, CXCL10, and CXCL11 were assessed using the chemokine bead array in conjunction with the flow cytometry, along with real-time PCR (RT-PCR). The transcription factors CREB, NF-κB and NFAT5 were also studied for their expressions. The analysis of pg/ml (picogram/milliliter) values was done by using LEGENDplex™ Data Analysis Software. RESULTS: The results obtained demonstrated early phase transient increase in CXCL-11, CCL20, CXCL9, CCL3, CCL2, CXCL10 and CXCL8. However, the expression of CCL3, CXCL10 and CXCL8 was higher in the late stage as compared to the early stage. The relative gene expression of CREB, NF-κB, NFAT5 were upregulated in the late stage of OSMF when compared to normal. CONCLUSION: Distinctive sets of chemokine expression during the early and late stages of OSMF suggest a unique pattern of disease progression playing an important role in the pathogenesis.
BACKGROUND: Oral submucous fibrosis (OSMF) is a chronic disease with significantly increasing malignant transformation rate. To date the pathogenesis of OSMF has been considered to be associated with areca nut constituents and their action on fibroblasts. However, fibrosis is also associated with immunological factors such as chemokines. In-depth analysis of such factors is the need of the hour in OSMF to better understand the pathogenesis so that effective therapeutic strategies can be developed in the future. MATERIALS AND METHOD: Clinically diagnosed cases of OSMF (n=21) and healthy individuals (n=10) were enrolled in the present study. Chemokines such as CCL2, CCL3, CCL4, CCL5, CCL11, CCL17, CCL28, CXCL1, CXCL5, CXCL8, CXCL9, CXCL10, and CXCL11 were assessed using the chemokine bead array in conjunction with the flow cytometry, along with real-time PCR (RT-PCR). The transcription factors CREB, NF-κB and NFAT5 were also studied for their expressions. The analysis of pg/ml (picogram/milliliter) values was done by using LEGENDplex™ Data Analysis Software. RESULTS: The results obtained demonstrated early phase transient increase in CXCL-11, CCL20, CXCL9, CCL3, CCL2, CXCL10 and CXCL8. However, the expression of CCL3, CXCL10 and CXCL8 was higher in the late stage as compared to the early stage. The relative gene expression of CREB, NF-κB, NFAT5 were upregulated in the late stage of OSMF when compared to normal. CONCLUSION: Distinctive sets of chemokine expression during the early and late stages of OSMF suggest a unique pattern of disease progression playing an important role in the pathogenesis.