Small-molecule inhibitors and the salivary gland epithelium in Sjögren’s syndrome
Sarah Pringle, Xiaoyan Wang, Hendrika Bootsma, Fred K. L. Spijkervet, Arjan Vissink & Frans G. M. Kroese
Received 27 Mar 2019, Accepted 11 Jun 2019, Published online: 16 Jun 2019
Download citation https://doi.org/10.1080/13543784.2019.1631796
In this article
ABSTRACT
1. Introduction: small-molecule inhibitor use in Sjögren’s syndrome
2. The salivary gland epithelium in Sjögren’s syndrome
3. Inhibitors of major immune signaling pathways
4. Manipulation of epithelial cell survival mechanisms
5. Conclusion
6. Expert opinion
References
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.
KEYWORDS: Epithelium, hyposalivation, inflammation, NFκB signaling, salivary gland, Sjögren’s syndrome, small-molecule inhibitors, toll-like receptor
In this article
Sarah Pringle, Xiaoyan Wang, Hendrika Bootsma, Fred K. L. Spijkervet, Arjan Vissink & Frans G. M. Kroese
Received 27 Mar 2019, Accepted 11 Jun 2019, Published online: 16 Jun 2019
Download citation https://doi.org/10.1080/13543784.2019.1631796
In this article
ABSTRACT
1. Introduction: small-molecule inhibitor use in Sjögren’s syndrome
2. The salivary gland epithelium in Sjögren’s syndrome
3. Inhibitors of major immune signaling pathways
4. Manipulation of epithelial cell survival mechanisms
5. Conclusion
6. Expert opinion
References
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.
KEYWORDS: Epithelium, hyposalivation, inflammation, NFκB signaling, salivary gland, Sjögren’s syndrome, small-molecule inhibitors, toll-like receptor
In this article
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