sPLA 2 -IIa participates in ocular surface inflammation in humans with dry eye disease

• Published in: Experimental eye research Vol. 201; p. 108209
• Main Authors: Wei, Y, Asbell, P A
• Format: Journal Article
• Language: English
• Published: England 01.12.2020
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers - metabolism; Cells, Cultured; Conjunctiva - metabolism; Dry Eye Syndromes - metabolism; Dry Eye Syndromes - pathology; Female; Humans; Inflammation - metabolism; Inflammation - pathology; Male; Middle Aged; Phospholipases A2, Secretory - metabolism; Tears - metabolism; Young Adult; sPLA-IIa; Conjunctival epithelium; Inflammation; Dry eye disease

To determine the roles of secretory phospholipase A2-IIa (sPLA -IIa) in the inflammatory responses of the compromised ocular surface. Conjunctival impression cytology (IC) samples and tears were collected from patients with mild to severe non-Sjogren's dry eye disease (DED) and normal controls. The IC samples were analyzed for transcription of sPLA -IIa and inflammatory cytokine/chemokine genes using quantitative real-time RT-PCR (qRT -PCR) and pathway-focus PCR-array. The tear samples were analyzed for 13 inflammatory cytokines and chemokines with Millipore 13-Plex kit. Finally, sPLA2-IIa-treated human conjunctival epithelial cell (HCjE) cultures were analyzed with a pathway-focused PCR array. Transcription of sPLA2-IIa was significantly increased in severe DED patients as compared to those of mild DED patients and normal controls. The transcription of inflammatory cytokines (IL-1β, IL-4, IL-6, IL-17, TNF-α, IFN-γ), chemokines (IL-8, CXCL10, CXCL11, CXCL-14, CCR6, LTB) and matrix metalloproteinase 9 (MMP9) were simultaneously increased in the same IC samples of DED. Concentrations of IL-6 and IL-8 in tears were significantly higher in DED patients than those of the controls and positively correlated to DED severity scores. On the other hand, IL-2, IL-4, IL-10, IL-12 and IFN-γ were significantly lower in DED patients than those in the controls and inversely correlated to DEWS scores. Single treatment of sPLA2-IIa, IL-1β or TNF-α of HCjE cells induced minimal to no PGE2 production. When sPLA2-IIa was added to HCjE cells that were pre-treated with pro-inflammatory cytokines (TNF-α or IL-1β), significant stimulation of PGE2 production was observed, concurrent with the extensive transcriptional changes of many inflammatory cytokines/chemokines and their receptors. sPLA -IIa activity was elevated and not only associated with inflammatory changes in DED patient samples, but was also found to cooperate with TNF- α and IL-1β to induce inflammatory response in human conjunctival epithelial cells. Understanding the roles of sPLA -IIa in ocular surface inflammation may lead to better strategies for the treatment of chronic inflammation associated with DED and other ocular inflammatory conditions.