TNFα (Tumor Necrosis Factor-alpha) is a cytokine involved in systemic inflammation and is a member of a group of cytokines that stimulate the acute phase reaction. TNFα Activators are chemical compounds that either directly or indirectly increase the expression or activity of TNFα. Lipopolysaccharide, for example, targets Toll-like receptor 4 (TLR4) and activates the NF-κB pathway, a known modulator for TNFα transcription. Protein Kinase C activators like PMA also stimulate NF-κB, elevating TNFα levels. Forskolin elevates cellular cAMP, which in turn has an effect on TNFα expression. Additionally, some compounds like Resveratrol and Curcumin interact with SIRT1 and Nrf2, respectively, to indirectly enhance TNFα expression.
Several other compounds are involved in the modulation of cellular stress and chromatin architecture. Thapsigargin induces endoplasmic reticulum stress, which can activate the unfolded protein response (UPR), another pathway that upregulates TNFα. Chromatin modifiers like Sodium Butyrate and Anacardic Acid make the gene locus more accessible for transcription, thereby influencing TNFα levels. Furthermore, compounds like Ionomycin and Capsaicin can affect intracellular calcium levels, an important second messenger in cellular signaling, leading to increased expression of TNFα. Overall, these chemicals act through various cellular mechanisms to modulate the activity or expression of TNFα.
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