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AB0144 Interleukin-17 Impairs Salivary Tight Junctions in Non-Obese Diabetic Mice
  1. L.-W. Zhang1,
  2. X. Cong2,
  3. G.-Y. Yu3,
  4. L.-L. Wu2,
  5. H. Hua1
  1. 1Department of Oral Medicine, Peking University School and Hospital of Stomatology
  2. 2Department of Physiology and Pathophysiology, Peking University Health Science Center
  3. 3Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China

Abstract

Background Sjögren's syndrome (SS) is an inflammatory autoimmune disease that causes secretory dysfunction of the salivary glands. It has been reported that pro-inflammatory cytokine interleukin-17 (IL-17) was elevated and tight junction (TJ) integrity was disrupted in minor salivary gland from SS patients. The aim of the research was to observe the alteration of TJs in salivary glands of non-obese diabetic (NOD) mice and explore the impact of IL-17 on TJs.

Objectives The aim of the research was to observe the alteration of TJs in salivary glands of non-obese diabetic (NOD) mice and explore the effect of IL-17 on TJs.

Methods 12-week-old female NOD mice and BALB/c mice were used. Stimulated salivary flow rate and histopathological changes were evaluated. The expression of TJ molecules and IL-17 in SMG and PG were detected by real-time PCR and western blot analysis. Immunohistochemistry was used to observe the distribution of TJ molecules and IL-17 in SMGs and PGs. In addition, the alternation of TJs under the stimulation of IL-17 (50 ng/ml) were evaluated in cultured SMG and PG tissues.

Results Lymphocyte infiltration was mainly observed in submandibular glands (SMGs), but not in parotid glands (PGs) of NOD mice (Fig. A). Likewise, IL-17 was significantly increased and mainly located in lymphocytic infiltrating regions in SMGs, but not detectable in PGs of NOD mice (Fig. B-D). Claudin-1 and -3 were elevated whereas claudin-4, occludin and zonula occludens-1 (ZO-1) were reduced in SMGs of NOD mice. However, no change in the expression of TJ proteins was found in PGs. In vitro, IL-17 significantly decreased the protein levels of claudin-4 and ZO-1 in the cultured SMG tissues, as well as claudin-1, occludin and ZO-1 in PG tissues.

Conclusions IL-17 derived from infiltrating lymphocyte impairs the integrity of TJ, and thus might contribute to salivary gland dysfunction in SS.

  1. Ewert P, Aguilera S, Alliende C, Kwon YJ, Albornoz A, Molina C, Urzúa U, Quest AF, Olea N, Pérez P, et al. 2010. Disruption of tight junction structure in salivary glands from Sjogren's syndrome patients is linked to proinflammatory cytokine exposure. Arthritis Rheum. 62(5):1280–1289.

  2. Katsifis GE, Rekka S, Moutsopoulos NM, Pillemer S, Wahl SM. 2009. Systemic and local interleukin-17 and linked cytokines associated with Sjögren's syndrome immunopathogenesis. Am J Pathol. 175(3):1167–1177.

  3. Nguyen CQ, Hu MH, Li Y, Stewart C, Peck AB. 2008. Salivary gland tissue expression of interleukin-23 and interleukin-17 in Sjögren's syndrome: findings in humans and mice. Arthritis Rheum. 58(3):734–743.

  4. Nguyen CQ, Yin H, Lee BH, Carcamo WC, Chiorini JA, Peck AB. 2010. Pathogenic effect of interleukin-17A in induction of Sjögren's syndrome-like disease using adenovirus-mediated gene transfer. Arthritis Res Ther. 12(6):R220.

Acknowledgement This study was supported by the National Natural Science Foundation of China [grant numbers 81371163 and 81300893]. The authors declare no competing financial interests.

Disclosure of Interest L.-W. Zhang Grant/research support from: National Natural Science Foundation of China [grant numbers 81371163 and 81300893], Consultant for: no, Employee of: no, Paid instructor for: no, Speakers bureau: no, X. Cong Grant/research support from: National Natural Science Foundation of China [grant numbers 81371163 and 81300893], Consultant for: no, Employee of: no, Paid instructor for: no, Speakers bureau: no, G.-Y. Yu Grant/research support from: National Natural Science Foundation of China [grant numbers 81371163 and 81300893], Consultant for: no, Employee of: no, Paid instructor for: no, Speakers bureau: no, L.-L. Wu Grant/research support from: National Natural Science Foundation of China [grant numbers 81371163 and 81300893], Consultant for: no, Employee of: no, Paid instructor for: no, Speakers bureau: no, H. Hua Grant/research support from: National Natural Science Foundation of China [grant numbers 81371163 and 81300893], Consultant for: no, Employee of: no, Paid instructor for: no, Speakers bureau: no

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