IL-22 regulation of functional gene expression in salivary gland cells
Tegan N. Lavoie,
Wendy C. Carcamo,
Arun Wanchoo,
Ashok Sharma,
Afife Gulec,
Kathleen M. Berg,
Carol M. Stewart,
Cuong Q. Nguyen
Affiliations
Tegan N. Lavoie
Department of Infectious Diseases and Pathology, University of Florida College of Veterinary Medicine, 2015 SW 16th Ave, Gainesville, FL 32611, USA
Wendy C. Carcamo
Department of Infectious Diseases and Pathology, University of Florida College of Veterinary Medicine, 2015 SW 16th Ave, Gainesville, FL 32611, USA
Arun Wanchoo
Department of Infectious Diseases and Pathology, University of Florida College of Veterinary Medicine, 2015 SW 16th Ave, Gainesville, FL 32611, USA
Ashok Sharma
Center for Biotechnology and Genomic Medicine, Georgia Health Sciences University, Augusta, GA 30912, USA
Afife Gulec
Department of Infectious Diseases and Pathology, University of Florida College of Veterinary Medicine, 2015 SW 16th Ave, Gainesville, FL 32611, USA
Kathleen M. Berg
Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, 1600 SW Archer Rd, Gainesville, FL 32610, USA; Center for Orphan Autoimmune Disorders, University of Florida College of Dentistry, 1600 SW Archer Rd, Gainesville, FL 32610, USA
Carol M. Stewart
Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, 1600 SW Archer Rd, Gainesville, FL 32610, USA; Center for Orphan Autoimmune Disorders, University of Florida College of Dentistry, 1600 SW Archer Rd, Gainesville, FL 32610, USA
Cuong Q. Nguyen
Department of Infectious Diseases and Pathology, University of Florida College of Veterinary Medicine, 2015 SW 16th Ave, Gainesville, FL 32611, USA; Center for Orphan Autoimmune Disorders, University of Florida College of Dentistry, 1600 SW Archer Rd, Gainesville, FL 32610, USA; Corresponding author at: Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, 2015 SW 16th Ave, V3-152 Gainesville, FL, 32611 USA.
ABSTRACT: TH17 cells and their associated signature cytokines, IL-17 and IL-22, are highly elevated in primary Sjögren's syndrome (pSjS). The levels of IL-22 present in sera showed significant correlations with many disease parameters, specifically hyposalivation, anti-SSB, anti-SSA/SSB, hypergammaglobulinemia and rheumatoid factor. The present study aims to examine the biological function of IL-22 on human salivary glands. To accomplish the goal, microarray analysis using the HumanHT-12 v4 Expression BeadChip was utilized to determine the biological function of IL-22. Differential expression analyses were conducted using the LIMMA package from the Bioconductor project. MTT assay, flow cytometry and Western blotting were used to identify the function of IL-22 on human salivary gland cells. Results indicate an extensive effect of IL-22 on many major molecular functions including activation of antimicrobial genes and downregulation of immune-associated pathways. Functional studies performed in-vitro using human salivary gland cells treated with IL-22 indicated a direct effect of IL-22 on cell cycling, specifically reducing cellular proliferation at the G2-M phase by activation of STAT3. These results suggest the important role of IL-22 in the salivary gland function. The present study suggests that IL-22 might be involved in regulating inflammation and controlling the cell proliferation in SjS. Keywords: IL-22, Cytokine, Sjogren's syndrome, Gene expression, Microarray