Besides regulating mycobacterial infection [53], p38 are also potent regulators of inducible NO generation [55], [56].
HO-1 has been shown to protect against cellular stress-associated physiological disorders on the basis of its rapid up-regulation under various stress conditions and potent physiological regulating properties.
Another potent way regulating NO synthesis is mediated by DDAH.
C5a is a potent chemokine regulating migration of cells in the innate immune system.
EPA and DHA were considered to be more potent in regulating immune function [ 14].
TGF-β1 is also a potent immunomodulator, regulating T-cell proliferation, differentiation and survival in healthy humans [ 12, 23] by downregulating IL-2 transcription via Smad3 [ 24] or by directly targeting cell cycle regulators such as cyclin-dependent kinase inhibitors (p15, p27 or p21), c-Myc, cyclin D2 and cyclin E [ 25].
For example, in mice mesenteric arteries, 8,9-EETs are the most potent for regulating vasorelaxation [ 36], whereas in rat kidneys, 8,9-EETs can be metabolized by COX enzymes to vasoconstrictor metabolites in pre-glomerular vessels [ 48], and in pulmonary arteries, 8,9-EETs8,9-EETse pulmonarterytery constriction [ 49].
miRNAs have been demonstrated to be potent to regulate stem cells differentiation [ 27, 39].
Following phosphorylation the R-Smads heterooligomerise with the co-Smad, Smad4, and accumulate in the nucleus where in conjunction with a number of cofactors they regulate target gene expression. 1 TGF-β acts as a potent immunosuppressor by regulating the proliferation and survival of many cells of the immune system.
