Inhibitory effect of GMI, an immunomodulatory protein from Ganoderma microsporum, on myofibroblast activity and proinflammatory cytokines in human fibrotic buccal mucosal fibroblasts

Abstract

Oral submucous fibrosis (OSF) has been indicated as one of the oral potentially malignant disorders. Epidemiological studies have attributed this pathological fibrosis to the habit of areca nuts chewing, which causes chronic inflammation and persistent activation of myofibroblasts in the oral cavity. Hence, it is crucial to find an effective intervention to ameliorate inflammation in order to prevent the malignant progression of OSF. In this study, we assessed the anti-inflammatory effect of the immunomodulatory protein, GMI, extracted from Ganoderma microsporum on the expression proinflammatory cytokines and the myofibroblast characteristics in human fibrotic buccal mucosal fibroblasts (fBMFs). Our results demonstrated that the expression level of interleukin (IL)-6 and IL-8 were decreased after exposure of GMI and the myofibroblast activities, including collagen gel contraction, migration, invasion, and wound healing abilities were inhibited as well. Furthermore, we confirmed these findings in the arecoline-stimulated BMFs. Consistent with the above findings, the expression of the myofibroblast marker a-smooth muscle actin and other fibrogenic markers, such as type I collagen, fibronectin, and vimentin in fBMFs were all reduced in a dose-dependent manner. Collectively, our data suggested that GMI suppressed the proinflammatory cytokines and myofibroblast features in fBMFs, and could serve as a promising and natural antifibrosis agent.

The Effect of Ganoderma Microsporum immunomodulatory proteins on alleviating PM2.5-induced inflammatory responses in pregnant rats and fine particulate matter-induced neurological damage in the offsprings

“…PM 2.5 leads to increases in the expression of proinflammatory factors 19 , thus intensifying oxidative stress. This study revealed that GMI administration reduced the expression of proinflammatory factors 25 , inflammatory responses, and oxidative stress in rats, and attenuated their offspring’s inflammatory response.…”

Arctigenin Reduces Myofibroblast Activities in Oral Submucous Fibrosis by LINC00974 Inhibition

“…Over the past few years, growing attention has been paid to the use of natural products against a variety of diseases, including fibrosis and cancers [20,21]. Our group has also demonstrated the effect of various natural compounds on the suppression of oral cancer or OSF via the reduction of inflammation or mesenchymal transdifferentiation [22,23,24,25]. Current evidence has suggested that TGF-β signaling is the key pathway to trigger the manifestation of OSF [7,8].…”

“…The resulting colored solution was evaluated spectrophotometrically at 570 nm. The data were presented as a percentage of DMSO [25]. As for MTS assay, MTS solution containing PES was added to each well after incubation with arctigenin.…”

Current Understanding of the Structure and Function of Fungal Immunomodulatory Proteins

“…FIP-lti1 and FIP-lti2 have been shown to mitigate ConA-induced liver oxidative injury ( 21 ). FIP-gmi was recently found to exert anti-inflammatory effects on neuron/glia cells ( 87 ), human fibrotic buccal mucosal fibroblasts ( 88 ), as well as intestinal mucosa and the tongue ( 89 ).…”