p38 MAPK Inhibitor NJK14047 Suppresses CDNB-Induced Atopic Dermatitis-Like Symptoms in BALB/c Mice

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disorder. Suppression of MAPKs and NF-κB is implicated as a vital mechanism of action of several traditional Chinese medicines for AD therapy. Although overexpression of MAPK mRNA in the skin tissue has been shown in the AD model, the roles of each MAPK in AD pathogenesis have rarely been studied. This study examined the effect of NJK14047, an inhibitor of p38 MAPKs, on AD-like skin lesions induced in BALB/c mice by sensitization and challenges with 1-chloro-2,4-dinitrobenzene (CDNB) on dorsal skin and ears, respectively. After induction of AD, NJK14047 (2.5 mg/kg) or dexamethasone (10 mg/kg) was administrated for 3 weeks via intraperitoneal injection. Following its administration, NJK14047 suppressed CDNB-induced AD-like symptoms such as skin hypertrophy and suppressed mast cell infiltration into the skin lesions. It also reduced CDNB-induced increase in TH2 cytokine (IL-13) and TH1 cytokines (interferon-γ and IL-12A) levels but did not decrease serum IgE level. Furthermore, NJK14047 blocked CDNB-induced lymph node enlargement. These results suggest that NJK14047, a p38 MAPK inhibitor, might be an optimal therapeutic option with unique modes of action for AD treatment.

Phosphorylated p38 MAP kinase expression by leucocytes is increased in allergic humans and associated with IgE responses

“…Our exploratory study should prompt further studies of these pathways and potential drug targets. Other research groups reported findings that support our hypothesis 4,19,20 . Lastly, the SB202190 inhibitor may have non‐specific effects on the cells studied.…”

“…Other research groups reported findings that support our hypothesis. 4,19,20 Lastly, the SB202190 inhibitor may have non-specific effects on the cells studied. Therefore, other approaches such as use of knockout mouse or CRISPR technology are necessary to confirm these putative drug targets.…”

Anti-inflammatory and immunomodulatory effects of polysaccharide extracted from Wuguchong (maggot) on 2,4-dinitrochlorobenzene-induced atopic dermatitis in mice

“…Phosphorylation of MAPKs leads to inflammatory mediators’ production and promotes the allergic inflammatory response ( Barnes, 2011 ; Arthur and Ley, 2013 ). Among the mitogen-activated protein kinases, p38 and ERK MAPK pathways are involved in the pathogenesis of inflammatory skin diseases including AD ( Johansen et al, 2005 ; Lee et al, 2022 ; Zeze et al, 2022 ), and the JNK pathway is also activated in atopic dermatitis ( Lu et al, 2018 ). Increasing evidence has demonstrated the efficacy of p38 and ERK MAPK inhibitors on AD, which may work as potential therapeutic targets ( Lee et al, 2022 ; Zeze et al, 2022 ).…”

“…Among the mitogen-activated protein kinases, p38 and ERK MAPK pathways are involved in the pathogenesis of inflammatory skin diseases including AD ( Johansen et al, 2005 ; Lee et al, 2022 ; Zeze et al, 2022 ), and the JNK pathway is also activated in atopic dermatitis ( Lu et al, 2018 ). Increasing evidence has demonstrated the efficacy of p38 and ERK MAPK inhibitors on AD, which may work as potential therapeutic targets ( Lee et al, 2022 ; Zeze et al, 2022 ). In the current study, PEW significantly inhibits the activation of p38, ERK, and JNK MAPKs ( Figure 8 ), not only contributing to the downregulation of the NF-κB signaling pathway but also blocking the production of inflammatory mediators, thus relieving skin inflammation in AD mice.…”

“…Phosphorylation of MAPKs leads to inflammatory mediators’ production and promotes the allergic inflammatory response ( Barnes, 2011 ; Arthur and Ley, 2013 ). And the MAPK pathways are involved in the pathogenesis of inflammatory skin diseases, including AD ( Johansen et al, 2005 ; Lu et al, 2018 ; Lee et al, 2022 ; Zeze et al, 2022 ).…”