Macrophage migration inhibitory factor contributes to the pathogenesis of benign lymphoepithelial lesion of the lacrimal gland

Abstract

BackgroundBenign Lymphoepithelial Lesion (BLEL) is a rare disease observed in the adult population. Despite the growing numbers of people suffering from BLEL, the etiology and mechanisms underlying its pathogenesis remain unknown.MethodsIn the present study, we used gene and cytokines expression profiling, western blot and immunohistochemistry to get further insight into the cellular and molecular mechanisms involved in the pathogenesis of BLEL of the lacrimal gland.ResultsThe results showed that Macrophage Migration Inhibitory Factor (MIF) was the most highly expressed cytokine in BLEL, and its expression positively correlated with the expression of Th2 and Th17 cells cytokines. MIF was found to regulate biological functions and pathways involved in BLEL pathogenesis, such as proliferation, resistance to apoptosis, MAPK and PI3K/Akt pathways. We also found that MIF promotes fibrosis in BLEL by inducing BLEL fibroblast differentiation into myofibroblasts as well as the synthesis and the deposit of extracellular matrix in BLEL tissues.ConclusionsOur findings demonstrate the contribution of MIF to the pathogenesis of BLEL of the lacrimal gland and suggested MIF as a promising therapeutic target for its treatment.Electronic supplementary materialThe online version of this article (10.1186/s12964-018-0284-4) contains supplementary material, which is available to authorized users.

Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition

“…Skin tissue at the wound site was harvested and fixed with formalin and embedded in paraffin blocks, and then 4 μm thick paraffin sections were mounted on glass slides for histological staining. IHC and IF of the paraffin-embedded tissue sections were performed as previously indicated [ 51 ]. Briefly, sections were dewaxed and rehydrated by subsequent immersion in xylene, ethanol (100%, 95%, 70%, and 50%) and deionized H 2 O. Antigen was then retrieved in citrate buffer, and non-specific staining between the primary antibodies (Table S1 A) and the tissue was blocked by incubation in 1% goat serum in PBS for 60 min at RT.…”

Molecular hydrogen promotes wound healing by inducing early extracellular matrix deposition and epidermal stem cell proliferation

“…Skin tissue at the wound site was harvested and xed with formalin and embedded in para n blocks, and then 4 μm thick para n sections were mounted on glass slides for histological staining. IHC and IF of the para n-embedded tissue sections were performed as previously indicated 93 . Brie y, sections were dewaxed and rehydrated by subsequent immersion in xylene, ethanol (100%, 95%, 70%, and 50%) and deionized H 2 O. Antigen was then retrieved in citrate buffer, and non-speci c staining between the primary antibodies (Table S1A) and the tissue was blocked by incubation in 1% goat serum in PBS for 60 minutes at RT.…”

Evaluation of the Efficacy of Immune and Inflammatory Markers in the Diagnosis of Lacrimal-Gland Benign Lymphoepithelial Lesion

“…Benign lymphoepithelial lesion, also known as Mikulicz disease, occurs in the parotid gland, lacrimal gland, and other sites and is characterized by lymphocyte infiltration associated with epithelial hyperplasia [ 1 , 2 ]. Lacrimal-gland benign lymphoepithelial lesion (LGBLEL) is an immune-related inflammatory lesion that is most common in middle-aged women [ 3 , 4 ]. The main manifestations are diffuse enlargement of the bilateral or unilateral lacrimal glands and eyelid swelling.…”

“…The main manifestations are diffuse enlargement of the bilateral or unilateral lacrimal glands and eyelid swelling. Typical pathological manifestations are diffuse infiltration of lymphocytes and plasma cells in the lacrimal tissue, atrophy and disappearance of glands, and hyperplasia of the fibrous tissue [ 3 , 4 ]. Studies have shown elevated immunoglobulin 4 (IgG4) expression levels in some LGBLEL serum and tissues; therefore, LGBLEL with positive IgG4 expression is considered IgG4-related ophthalmic disease (IgG4-ROD) [ 5 ].…”