Atorvastatin inhibits the inflammatory response caused by anti-M3 peptide IgG in patients with primary Sjögren’s syndrome

Abstract

Experimental and clinical investigations have revealed that statins can down-regulate acute and chronic inflammatory processes. Whether statins express anti-inflammatory activities in the salivary glands in patients with primary Sjögren's syndrome (pSS) is not known. The in vitro and in vivo effect of atorvastatin on rat submandibular gland treated with anti-M(3) peptide IgG purified from SS patients was studied. The anti-inflammatory effects of atorvastatin were assessed by measuring the levels of IL-1β, PGE(2) and MMP-3 by ELISA. Atorvastatin inhibited the increase in the production of IL-1β, PGE(2) and MMP-3 in submandibular glands treated with anti-M(3) peptide IgG. A positive correlation between IL-1β production with accumulation of PGE(2) and MMP-3 was observed. Rats pre-treated orally with atorvastatin (30 mg kg(-1)) or vehicle (phosphate-buffered solution) once a day for three consecutive days impaired the increment in the production of IL-1β, PGE(2) and MMP-3 in the submandibular gland in the presence of anti-M(3) peptide IgG. In conclusion, the anti-inflammatory effects of atorvastatin are dependent upon inhibition of production of a pro-inflammatory cytokine (IL-1β) and pro-inflammatory mediators such as PGE(2) and MMP-3. These data suggest that atorvastatin may constitute an anti-inflammatory effect in SS.

The Significance of Matrix Metalloproteinases in Oral Diseases

“…Humans (and mice) have three pairs of glands: the parotid glands (which are the largest), the sublingual glands and the submandibular macroscopic glands [40]. Sometimes a systemic autoimmune disease called Sjögren's syndrome (SS) attacks and damages the exocrine glands, which causes a loss of salivary and lachrymal secretion [41]. The etiology remains unknown, but immunological hyperactivity of anti-Ro and anti-La autoantibodies plays a primary role in the pathogenesis of this illness.…”

“…The etiology remains unknown, but immunological hyperactivity of anti-Ro and anti-La autoantibodies plays a primary role in the pathogenesis of this illness. Additionally, in the inflammatory process, aggregations of lymphocytes are initially periductal, but then become panlobular [41,42]. Immunoglobulin G (IgG) stimulates the production of IL-1b, PGE2, MMP-3 and MMP-9.…”

“…MMP-3 (stromelysin-1) is able to degrade proteoglycans, some types of collagen, laminin, fibronectin, gelatin and elastin. It also activates other members of the MMP family, such as MMP-1 and MMP-9, increasing the destructive effect on ECM components [41][42][43]. The implication of metalloproteinases, including MMP-2 and -9, has been proved in the nonobese diabetic (NOD) mouse model of Sjögren's syndrome that is frequently used as a spontaneous animal model of this disorder [44].…”

Action of anti‐M3 muscarinic acetylcholine receptor IgG of primary Sjögren's syndrome on the enzymatic antioxidant system in rat submandibular gland

“…Many autoantibodies, including rheumatoid factor (RF), antinuclear antibody (ANA) and antibodies to SSA/Ro or SSB/La, have reportedly been detected in the case of both pSS and aSS . Recent studies have proved that the antibody to M 3 subtype muscarinic acetylcholine receptors (M 3 mAChR) is a good serum marker in pSS .…”

Autoantibodies against Muscarinic Acetylcholine Receptor on Exocrine Glands in Sjögren Syndrome

“…Relevant in this sense, are those theories shifting their attention to the organ specific immunological deregulation involved in the manifestations and the chronic course of the disease [4][5][6][7], and to the clinical features of an immunological or inflammatory disease [8,9].…”