Abstract:
INTRODUCTION:The salivary gland (SG) in primary Sjögren's syndrome (pSS) is characterized by its lack of function (hyposalivation) and lymphocytic invasion. Small-molecule inhibitors (SMIs) are a new class of drugs, whose diminutive size permits diffusion into cells. SMIs targeting components of the immune system are eagerly being trialed for their potential therapeutic utility in pSS. Neglected until now, however, is a discussion of the potential effects of SMIs on the SG epithelium. AREAS COVERED:We begin by reminding the reader of the SG epithelial compartment, its complicity in inflammatory milieu formation in pSS, and categories of SMIs which merit attention. We discuss each SMI category, including pre-clinical data concerning pSS and likely consequences of their application on the SG epithelium. EXPERT OPINION:Recovery of saliva production in pSS requires restoring the function of the SG epithelium, not solely on inflammation resolution. Many SMIs, for example, those blocking JAK-STAT signaling, interfere with critical epithelial cell pathways, most notably EGF signaling. If the effect of SMIs on SG epithelium is ignored, recovery of SG function will be challenging. We predict that NFκB signaling blockade will impart the least SG epithelium damage whilst reducing inflammation and facilitating recovery from hyposalivation in pSS.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Pringle S,Wang X,Bootsma H,Spijkervet FKL,Vissink A,Kroese FGMdoi
10.1080/13543784.2019.1631796subject
Has Abstractpub_date
2019-07-01 00:00:00pages
605-616issue
7eissn
1354-3784issn
1744-7658journal_volume
28pub_type
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journal_title:Expert opinion on investigational drugs
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