Fig. 8

A proposed comprehensive working model.

A detailed working model depicting the role of TRPA1 in 17-AAG mediated regulation of inflammation in LPS or PMA stimulated macrophages. TRPA1 is modulated upon LPS/PMA stimulation (A). pro-inflammatory responses including IL-6, TNF, MHCII, CD80/86, NO, intracellular calcium, and intracellular signaling proteins p38-MAPK, p-ERK 1/2, p-SAPK-JNK are significantly upregulated with LPS (A.1) or PMA stimulation (A.2). Upon administration of 17-AAG along with LPS or PMA, the pro-inflammatory responses are downregulated (C). Inhibition of TRPA1 via HC-030031 with 17-AAG and LPS or PMA administration reverses the pro-inflammatory responses, intracellular signaling proteins p38-MAPK, p-ERK 1/2, p-SAPK-JNK back to the LPS or PMA stimulated levels with a further diminished intracellular calcium level (B). Activation of TRPA1 via AITC and 17-AAG in LPS or PMA stimulated macrophages by impairing the proinflammatory responses, intracellular calcium, and intracellular signaling proteins p-p38-MAPK, p-ERK 1/2, p-SAPK-JNK to a greater extent exhibiting an anti-inflammatory property (D). The pro-inflammatory responses are represented according to the color code.