Mediated intracellular signaling MAPK pathway

Bromelain is a mixture of cysteine proteases obtained from pineapple stems (Ananas comosus, Bromeliaceae) that has been used therapeutically for the treatment of inflammation and trauma [119]. 7n vitro, it has varied stimulatory effects on leukocyte populations, increases CD2-mediated T cell activation, enhances Ag-independent binding to monocytes, etc. The effects of bromelain have previously been attributed to its degradative action at cell surfaces. However, it also acts independent of the removal of cell surface molecules [120]. In order to investigate the possible hormonelike effects of bromelain on intracellular signalling, its effects on TCR7CD3 signalling and IL-2 production were studied. It was observed that bromelain inhibits ERK-2 activation in ThO cells stimulated via the TCR, or with combined TPA plus calcium ionophore. In addtion, bromelain decreased IL-2, IFN-y, and IL-4 mRNA accumulation in ThO cells stimulated with TPA plus calcium ionophore, while the cytokine mRNA accumulation in cells stimulated via TCR was not affected. It seems that bromelain does not act on ERK-2 directly but also inhibits p2r activation, an effector molecule upstream from ERK-2 in the Raf-1/MEKl/ERK kinase cascade. Since p21 is an effector for multiple MAPK pathways, it is likely that bromelain affects other MAPK signalling cascades, such as the INK pathway or p38 MAPK pathway [121],... 

Exposure of normal human epidermal keratinocytes (NHEK) to UVB radiation induces intracellular release of hydrogen peroxide (oxidative stress) and phosphorylation of MAPK cell-signaling pathways. Pretreatment of NHEK with EGCG inhibits UVB-induced hydrogen peroxide production and its mediated phosphorylation of MAPK signaling pathways [16]. It has been demonstrated that tea polyphenols inhibited PKC, MAPK, and AP-1 activities in NIH 3T3 cells [17]. 

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