Salivary Flow is Regulated via IP3 Receptor in a Type I Interferon Response

Salivary Flow is regulated via IP3 Receptor in a Type I Interferon Response

James M Roger, DDS, MS¹, Kamil Alzayady, PhD², David Yule PhD², Antonia Kolokythas, DDS, MS¹

¹ Dept. of Oral and Maxillofacial Surgery, University of Rochester School of Medicine and Dentistry, Rochester, NY; ² Department of Physiology, University of Rochester, Rochester, NY,

 Purpose: The primary purpose of salivary glands is to produce saliva; a fluid consisting of water, electrolytes and proteins which is essential to the well being and proper functioning of the oral cavity. Fluid flow is severely diminished in the patient suffering from Sjögren’s Syndrome (SS). It has been proposed that a viral infection may contribute or be a trigger for SS and in mice it has been shown that activation of Toll-like Receptor 3 (TLR3) causes reduction in salivary flow. Saliva secretion is closely tied to the concentration and flow of intracellular [Ca²⁺], and it has also been shown that in patients with SS, the Inositol Trisphosphate Receptor (IP3R) mediates the reduction in intracellular [Ca²⁺]. This report includes preliminary results and specifies future directions to further investigate if the defect in salivary flow in a Type I interferon response is mediated through the IP3R.

Methods: 12-week old C57BL/6J female mice were injected with the TLR3 ligand, Polyinosinic-polycytidylic acid (Poly (I:C)) to simulate a Type I Interferon response. Submandibular and parotid glands were collected after euthanasia and these were rapidly lysed and homogenized over 30 minutes. The lysate was subject to western blot including probing for the three IP3 Reception subtypes, R1, R2, and R3.

Results: In preliminary experiments at day 3, expression of the three IP3 receptor subtypes was detected in the experimental and control mouse parotid and submandibular glands. This early result is being tested at additional time points and Ploy (I:C) doses.

Conclusions: These early results suggest that the regulation and the function of the IP3 receptor and calcium signaling may be altered in a systemic Type I Interferon Response. We continue to evaluate the expression of IP3 receptor in the salivary glands with other models of chronic and acute inflammation to further understand the impact this may have in the autoimmune disease, SS. We will present these ongoing results for review and discussion.

References:

Teos L Y, Zhang Y, Cotrim AP, Swaim W, Won JH, Ambrus J, Shen L, Bebris L, Grisius M, Jang SI, Yule DI, Ambudkar IS and Alevizos I: "IP3R deficit underlies loss of salivary fluid secretion in Sjogren's Syndrome." Sci Rep 5: 13953, 2015.

Nandula, S. R., P. Dey, K. L. Corbin, C. S. Nunemaker, H. Bagavant and U. S. Deshmukh: "Salivary gland hypofunction induced by activation of innate immunity is dependent on type I interferon signaling." J Oral Pathol Med 42(1): 66-72, 2013.