Silencing of miR‑155 suppresses inflammatory responses in psoriasis through inflammasome NLRP3 regulation

Abstract

Psoriasis is a dermatosis with the major clinical symptoms of scale, erythema and itching, and it has a long disease course. In addition, it is easily recurrent and refractory, greatly affecting the physical and mental health of patients. In the present study, it was hypothesized that the function of miR‑155 increases psoriasis‑induced inflammation and that its expression may be dependent on inflammasome activation. miR‑155 expression was examined by gene chip array and quantitative polymerase chain reaction analysis. miR‑155 expression levels were significantly increased in an in vivo model of psoriasis compared with normal tissues, as was the expression of NLR family pyrin domain containing 3 (NLRP3). In vitro, using keratinocyte‑induced HaCaT cells as a model for psoriasis, silencing of miR‑155 was confirmed to significantly decrease inflammation and NLRP3/caspase‑1 signaling. Activation of toll‑like receptor 4 (TLR4) enhanced the miR‑155‑induced inflammatory response in the in vitro keratinocyte model. Treatment with a TLR4 inhibitor or an NLRP3 inhibitor reversed the miR‑155‑mediated inflammation in the same cell system. The present study demonstrated that miR‑155 silencing suppressed psoriasis‑associated inflammatory responses through inflammasome NLRP3 regulation.

The Inflammasome Signaling Proteins ASC and IL-18 as Biomarkers of Psoriasis

“…Furthermore, besides analyzing protein levels, in future studies we will also analyze miRNAs that have been shown to affect inflammasome signaling (Wang et al, 2009;Pan et al, 2018;Cho et al, 2020) since miRNAs in extracellular vesicles have been recently shown to be useful biomarkers of psoriasis (Wang et al, 2020), and we have shown that inflammasome proteins in extracellular vesicles are good biomarkers of stroke (Kerr et al, 2018a). For instance, silencing of miR-155 is able to downregulate inflammasome signaling in Ps; thus, suggesting that miRNAs play an important role in Ps (Luo et al, 2018).…”

The Role of NLRP1, NLRP3, and AIM2 Inflammasomes in Psoriasis: Review

“…Diaz-Perez et al confirmed that IL-23 and extracellular ATP may activate P2 × 7R to trigger the development of psoriasis. Moreover, Diaz-Perez et al found that, the P2 × 7R-induced inflammatory response is mostly dependent on activation of NLRP3 [ 27 , 30 ]. Furthermore, they showed that activation of the NLRP3 inflammasome occurred mostly through neutrophils and not keratinocytes or T cells [ 30 ].…”

The Role of Epigenetics in Autoimmune/Inflammatory Disease

“…Overexpression of miR-155 in HaCaT keratinocytes results in increased NLRP3 and caspase-1 expression in response to priming with lipopolysaccharide. Authors concluded that this indicates positive effects of miRNA-155 on inflammasome activity and that this mechanism may centrally be involved in innate immune activation in psoriatic skin (98).…”

“…Thus, increased miR-21 expression in SLE may resemble another contributor to previously discussed increased IL-10 levels (114). The second target identified, miR-155, can contribute to increased inflammasome activation as found in the context of psoriasis (above) through enhanced expression of NLRP3 and caspase-1 (98), thus reflecting another example for the coexistence and interconnection of autoinflammatory and autoimmune mechanisms in SLE. Furthermore, kidney biopsies allow comparison of epigenetic events in affected renal tissue and show downregulation of miR-23b and upregulation of miR-146a when compared to unaffected renal tissue from patients with kidney cancer (115).…”