TLR2 signals via NF-κB to drive IL-15 production in salivary gland epithelial cells derived from patients with primary Sjögren's syndrome.
Toll-like receptors (TLRs) are pattern recognition receptors linking innate and adaptive immune responses, which resulted overexpressed in primary Sjögren's syndrome (pSS). Interleukin-15 (IL-15) is a pro-inflammatory cytokine which was recently demonstrated to be involved in pSS pathogenesis. The study was undertaken to clarify whether TLR2 is involved in the production of IL-15 in human salivary gland epithelial cells (SGEC) from pSS patients. SGEC primary cell cultures were established from pSS minor salivary gland tissues explanted from patients with a sure diagnosis of SS. After neutralization of TLR2 with a blocking monoclonal antibody, IL-15 production was assayed by immunoblotting and flow cytometry, IL-15 in the culture supernatants was measured by ELISA, and mRNA levels were assessed by RT-PCR and real-time PCR. The production of IL-15 by pSS SGEC decreased in culture supernatants and in protein lysates (p < 0.01) when TLR2 signaling was inhibited in pSS SGEC. In addition, a control at the transcriptional level was also detected; in fact, inhibition of nuclear factor (NF)-κB through the transfection of pSS SGEC with the dominant-negative inhibitory κBα proteins (IκBα) vector (IκBαDN) abrogated the stimulatory effect of TLR2 on IL-15 production. These data suggest that TLR2 activation is involved in the induction of IL-15 production by pSS SGEC and promotes inflammation through NF-κB activation. Therefore, therapeutic strategies that target TLR2/IL-15 pathway might be strong candidates for preventing or treating pSS.
Laboratory of Cell Biology, Section of Human Anatomy and Histology, Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Medical School, Piazza Giulio Cesare 1, 70124, Bari, Italy. margherita.sisto@uniba.it.
Margherita
M
Sisto
Laboratory of Cell Biology, Section of Human Anatomy and Histology, Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Medical School, Piazza Giulio Cesare 1, 70124, Bari, Italy.
Loredana
L
Lorusso
Laboratory of Cell Biology, Section of Human Anatomy and Histology, Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Medical School, Piazza Giulio Cesare 1, 70124, Bari, Italy.
Sabrina
S
Lisi
D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D019409:Interleukin-15 / Q000032:analysis*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D012469:Salivary Glands / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000473:pathology* / Q000503:physiopathology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
C569274:IL15 protein, human; D019409:Interleukin-15; D016328:NF-kappa B; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2
IL-15; Inflammation; NF-κB; Sjögren’s syndrome; Toll-like receptors