The study aimed to investigate the levels of proinflammatory (TNF-<i>α</i> and IL-6) along with anti-inflammatory cytokine IL-10 in patients with NASH and to correlate the cytokines' level with their polymorphism.
CGS21680 inhibited NASH development in steatotic mice and decreased cytokines and chemokines involved in Th cell recruitment or polarization (namely CXCL10, CCL2, tumor necrosis factor alfa [TNFα], tumor growth factor [TGFβ], and IL-12).
The results showed that genistein could reduce TLR4 protein and gene expression, decrease the endotoxin and TNFα, alleviate the inflammatory reaction and make the indicators detected in blood and liver stay near normal in NASH rats.
Meanwhile, our study suggests that restoration of systemic and intestinal vitamin D deficiency using by chronic vitamin D treatment effectively reduces TNFα-mediated immunological abnormalities associated with the gut-adipose tissue-liver axis and hepatic steatosis in NASH rats.
The serum levels of TNF-α and IL-6 were significantly increased in the novel NASH model group, and mice in this group exhibited histopathological features and insulin resistance reflective of NASH, i.e., macrovesicular hepatic steatosis, ballooning hepatocytes, Mallory-Denk bodies, lobular inflammation and fibrosis.
Inflammatory (TNF, LPS, IL-6) and profibrotic mediators (TGF-beta) do not regulate TUBA8 in HepG2 cells, primary HSC and the HSC cell line LX-2, when stimulated for 24 h. Agonists of the farnesoid X receptor and peroxisome proliferator activated receptor gamma, which are nuclear receptors involved in NASH and HCC pathophysiology, have no effect on TUBA8 in HepG2 and LX-2 cells.
Ablation of TNFα in miR-378-treated mice impaired the ability of miR-378 to facilitate hepatic inflammation and fibrosis, suggesting that TNFα signaling is required for miR-378 to promote NASH.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily, and has been identified as a novel mediator of fatty liver disease (FLD).
However, GTE in HF mice decreased biochemical and histological parameters of NASH and lowered hepatic p65 phosphorylation in association with decreased serum TNFα, mRNA expression of TNFR1 and TLR4 and MyD88 protein.
Mean serum TNFα levels were elevated in the serum of simple steatosis and NASH patients compared to healthy controls, reaching significance in NASH patients.
Previously, we have shown that the adipocyte-specific nuclear form of sterol regulatory element-binding protein-1c (nSREBP-1c) transgenic mice spontaneously developed hepatic lesions that are similar to those of human nonalcoholic steatohepatitis (NASH) with a concomitant elevation of plasma TNF-α.
Exposure of these cells to lipogenic (insulin, glucose, fatty acids) and pro-inflammatory factors (IL-1β, TNF-α, TGF-β) resulted in a characteristic NASH response, as indicated by intracellular lipid accumulation, modulation of NASH-specific gene expression, increased caspase-3/7 activity and the expression and/or secretion of inflammatory markers, including CCL2, CCL5, CCL7, CCL8, CXCL5, CXCL8, IL1a, IL6 and IL11.
The positive effects observed for SAR on NASH are due to the downregulation of the LPS/TLR4 pathway, as indicated by the suppression of hepatic Toll-like receptor 4 (TLR4), NF-κB, TNF-α, and transforming growth factor-β1 (TGF-β1) expression.
Thus, MetS-induced NASH in HFD rabbits plays an active role in the pathogenesis of ED, likely through TNFα, as indicated by treatments reducing liver and circulating TNFα levels (T or OCA), or neutralizing TNFα action (infliximab), which significantly improve penile responsiveness to Ach in HFD rabbits.
The area under the receiver operating characteristic (AUROC) of the pyroglutamate levels of NASH versus SS patients was more than those of tumor necrosis factor-α, adiponectin and interleukin-8.
As the disruption of endoplasmic reticulum (ER) homeostasis is linked to animal models of fatty liver disease, we investigated the effects of these OT models on the proteins related to ER stress (i.e., BiP, inositol-requiring enzyme 1, protein kinase RNA-like endoplasmic reticulum kinase, eIF2alpha, ATF6beta, and glucose-regulated protein 94) and apoptosis (C/EBP-homologous protein, Caspase-3, 4, and 12, Bax, and tumor necrosis factor receptor-associated factor 2) in livers of C57BL/6 mice.
AMSC-EVs significantly decreased the number of Kupffer cells (KCs) in the liver of rats with NASH and the mRNA expression levels of inflammatory cytokines such as tumor necrosis factor- (<i>Tnf-</i>) <i>α</i>, interleukin- (<i>Il-</i>) <i>1β</i> and <i>Il-6</i>, and transforming growth factor- (<i>Tgf-</i>) <i>β</i>.