The inhibition of p38 MAPK blocked inflammation to restore the functions of rat meibomian gland epithelial cells

Meibomian glands (MGs) are vital for ocular surface health. However, the roles of inflammation in the progression of meibomian gland dysfunction (MGD) are largely unknown. In this study, the roles of the inflammation factor interleukin-1 beta (IL-1 beta) via the p38 mitogen-activated protein kinases (MAPK) signaling pathway on rat meibomian gland epithelial cells (RMGECs) were explored. Eyelids from adult rat mice at 2 months and 2 years of age were stained with specific antibodies against IL-1 beta to identify inflammation levels. RMGECs were exposed to IL-1 beta and/or SB203580, a specific inhibitor of p38 MAPK signaling pathway, for 3 days. Cell proliferation, keratinization, lipid accumulation, and matrix metalloproteinases 9 (MMP9) expression were evaluated by MTT assay, polymerase chain reaction (PCR), immunofluorescence staining, apoptosis assay, lipid staining, and Western blot analyses. We found that IL-1 beta was significantly higher in the terminal ducts of MGs in rats with age-related MGD than in young rats. IL-1 beta inhibited cell proliferation, suppressed lipid accumulation and peroxisome proliferator activator receptor gamma (PPAR gamma) expression, and promoted apoptosis while activating the p38 MAPK signaling pathway. Cytokeratin 1 (CK1), a marker for complete keratinization, and MMP9 in RMGECs were also up-regulated by IL-1 beta. SB203580 effectively diminished the effects of IL-1 beta on differentiation, keratinization, and MMP9 expression by blocking IL-1 beta-induced p38 MAPK activation, although it also inhibited cell proliferation. The inhibition of the p38 MAPK signaling pathway blocked IL-1 beta-induced differentiation reduction, hyperkeratinization, and MMP9 overexpression of RMGECs, which provides a potential therapy for MGD.

Automated summary

This study investigated the roles of interleukin-1 beta (IL-1 beta) and the p38 mitogen-activated protein kinases (MAPK) signaling pathway in meibomian gland dysfunction (MGD) in rats. It was found that IL-1 beta levels were significantly higher in the terminal ducts of MGD rats compared to young rats. IL-1 beta inhibited cell proliferation, lipid accumulation, and peroxisome proliferator activator receptor gamma (PPAR gamma) expression, and promoted apoptosis by activating the p38 MAPK signaling pathway. SB203580, a specific inhibitor of p38 MAPK, effectively attenuated the effects of IL-1 beta on differentiation, keratinization, and MMP9 expression.