Hepatic toll‐like receptor 4 expression is associated with portal inflammation and fibrosis in patients with NAFLD

Abstract

TLR4 expression by regenerating and inflammatory cells at the porto-septal and interface level, favoured by increased LPS activity, is associated with activation of fibrogenic cells and the degree of fibrosis.

Portal inflammation during NAFLD is frequent and associated with the early phases of putative hepatic progenitor cell activation

“…Traditionally, the key characteristic features of NAFLD have been noted in centrolobular location, which may be consistent with the metabolic zonation within the liver acinus,3 while periportal changes have been less frequently described, as discussed by Vespasiani-Gentilucci et al 4. More recently, portal tract inflammation has gained the attention of NAFLD investigators, being recognised in a significant proportion of cases and, even more importantly, showing a strong association with the advanced forms of disease 5 6.…”

“…Immunohistochemistry was performed on sections obtained from formalin-fixed tissue embedded in paraffin. For the identification of putative hepatic progenitor cells, intermediate hepatobiliary cells, bile ductules and interlobular bile ducts, the primary antibody used were anti-CK-7, anti-CK-19 and anti-EpCAM 4. For the identification of activated hepatic stellate cells and portal/septal myofibroblasts, the primary antibody used was anti-α-SMA 4.…”

“…For the identification of putative hepatic progenitor cells, intermediate hepatobiliary cells, bile ductules and interlobular bile ducts, the primary antibody used were anti-CK-7, anti-CK-19 and anti-EpCAM 4. For the identification of activated hepatic stellate cells and portal/septal myofibroblasts, the primary antibody used was anti-α-SMA 4. Immunofluorescent staining was performed on representative samples in order to better characterise putative hepatic progenitor cells, bile ductules and interlobular bile ducts using anti-CK-7, and, in a subgroup of 24 patients, anti-CK-19 and anti-EpCAM antibodies in double labelling experiments (see online supplementary data for specifications concerning antibodies used and procedures).…”

Toll-Like Receptor 4 Expression in Human Breast Implant Capsules

“…13,20 As a consequence, toll-like receptors act as inflammatory modulators during both sterile and nonsterile wound healing processes, with evidence suggesting their role as a sensitive detection system to initiate tissue repair after injury. 9,35 Among these, toll-like receptor 4 is involved in a variety of fibrotic processes in kidney, 36 liver, 37,38 and skin. 12 It may be expressed by fibroblasts, 12 and its activation induces the transition to myofibroblasts.…”

Novel role of TLR4 in NAFLD development: Modulation of metabolic enzymes expression

“…Some studies also address that increased TLR4 expression is related to NASH progression [19][20][21].…”