Aberrant histone modification and inflammatory cytokine production of peripheral CD4+ T cells in patients with oral lichen planus

Abstract

Backgrounds To investigate alterations in histone modification and histone deacetylases ( HDAC s) in patients with oral lichen planus ( OLP ), and to evaluate correlations with inflammatory cytokine production. Methods Global histone H3/H4 acetylation and HDAC activity in CD 4+ T cells from 23 patients with OLP and 10 healthy control subjects were examined using spectrophotometry. The mRNA levels of eight members of four classes of HDAC genes were measured by real‐time quantitative polymerase chain reaction. Forty cytokines involved in inflammation were examined with a cytokine array. The correlation between histone modification and cytokine production was analyzed. Results Global histone H3 hypo‐acetylation was observed in OLP patients. Patients with OLP had significantly higher HDAC s activity,and higher HDAC 6 and HDAC 7 m RNA level compared with the controls. Of the 40 cytokines in the cytokine array, eight were significantly increased in OLP patients: interleukin ( IL )‐4, IL ‐8, IL ‐1ra, tumor necrosis factor receptor II ( TNFR II ), macrophage inflammatory protein 1b ( MIP ‐1b), fibrosis‐associated tissue inhibitors of metalloproteinase 1 ( TIMP )‐1, monocyte chemotactic protein 1 ( MCP ‐1), and eotaxin‐2. In the OLP group, the acetylation level of histone H3 was negatively correlated with IL ‐4 and MCP ‐1 production, and the expression of HDAC 6 mRNA was positively correlated with MCP ‐1 production. In the non‐erosive subgroup, acetylation of histone H3 was negatively correlated with IL ‐4, IL ‐16, and TIMP ‐2 production. In the erosive OLP subgroup, the expression of HDAC 7 mRNA was positively correlated with MIP ‐1a production. Conclusion Aberrant histone modification of CD 4+ T cells in peripheral blood could occur in OLP patients, and possibly affects inflammatory cytokine production.

The presence of Prevotella melaninogenica within tissue and preliminary study on its role in the pathogenesis of oral lichen planus

“…Previous studies proposed that tumor‐associated macrophages played a role in promoting inflammation in the development of OLP (Sato et al., 2006; Vered et al., 2013). More macrophage signals and NF‐κB signals were detected in the affected lesions and the peripheral blood of the OLP patients (Sato et al., 2006; Shen et al., 2019; Vered et al., 2013). Co‐culture of P. melaninogenica with mouse macrophages revealed that P. melaninogenica can adhere to the surface of macrophages and also invade macrophages.…”

“…The Toll‐like receptor 4 (TLR4) on the surface of macrophages recognized the lipopolysaccharide (LPS) of gram‐negative bacteria, then activated the mitogen‐activated protein kinase (MAPK) or nuclear factor kappa light‐chain enhancer of activated B cells (NF‐κB) signaling pathway, and finally triggered the transcription of pro‐inflammatory or anti‐inflammatory factors during the immune response (Ostareck & Ostareck‐Lederer, 2019). Macrophage markers were increased both in OLP lesions and in peripheral blood (Motta et al., 2018; Shen et al., 2019). TLR4 expression was elevated in OLP epithelium compared with normal controls (Siponen et al., 2012; Zeng et al., 2018), and NF‐κB signaling in the OLP lesions was over‐activated (Ge et al., 2012; Zhou et al., 2009).…”

“…NF-κB signals were detected in the affected lesions and the peripheral blood of the OLP patients(Sato et al, 2006;Shen et al, 2019;Vered et al, 2013). Co-culture of P. melaninogenica with mouse macrophages revealed that P. melaninogenica can adhere to the surface of macrophages and also invade macrophages.…”

Salivary cytokine profile in patients with oral lichen planus

“… 5 , 6 , 7 On antigen stimulation, CD4 + T cells differentiate into distinct subsets, each of which secrete certain cytokines. 8 Previous studies indicate that the cytokine expression profile is altered in OLP patients, especially the expression of Th1-, Th2-, and Th17-associated cytokines; 5 , 6 , 7 however, only a limited number of cytokines were implicated and the findings were inconsistent. 9 , 10 , 11 , 12 …”

Role of interleukin-4 in pathogenesis of oral lichen planus: A systematic review

“…-Search strategies The PubMed (MEDLINE) database of the United Finally, 28 studies were evaluated. Of the 28 articles evaluated, 14 articles evaluated the IL-4 levels in the different samples, which are detailed in Table 1 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25); nine articles evaluated the effect of different factors on the production of IL-4 that also shown in Table 2 (26)(27)(28)(29)(30)(31)(32)(33)(34). One article examined the polymorphism of the IL-4 gene in patient with lichen planus, one article about the amount of IL-4 producing cells; one article examined the effect of IL-4 on CD 275+ cells and one article compared IL-4+ T cells levels between OLP and SCC specimen.…”