Tissue-type Plasminogen Activator (tPA) Promotes M1 Macrophage Survival through p90 Ribosomal S6 Kinase (RSK) and p38 Mitogen-activated Protein Kinase (MAPK) Pathway

Abstract

Background: Macrophages become resistant to apoptosis in response to pathogenic cues. Results: Tissue-type plasminogen activator (tPA) protects the classically activated macrophages from apoptosis. Conclusion: tPA is an endogenous factor that promotes macrophage survival. Significance: tPA modulates inflammation by promoting the survival of polarized macrophages through a new signaling cascade.

Plasmin and plasminogen induce macrophage reprogramming and regulate key steps of inflammation resolution via annexin A1

“…42 Conversely, other studies suggest that the tissue-type plasminogen activator may promote the development of inflammatory macrophages. 43,44 In this study, we found that either Plg or Pla injected into the pleural cavity of mice did not change M1 macrophage numbers, but increased the number of M2 and Mres macrophages. Moreover, we observed decreased expression of the M1 marker iNOS and increased expression of the M2 markers CD206 and Arg-1 and the secreted products TGF-b and IL-6 in the pleural cavity.…”

Ferulic Acid Administered at Various Time Points Protects against Cerebral Infarction by Activating p38 MAPK/p90RSK/CREB/Bcl-2 Anti-Apoptotic Signaling in the Subacute Phase of Cerebral Ischemia-Reperfusion Injury in Rats

“…Accumulating evidence has indicated that activated ERK1/2 phosphorylates p90RSK and subsequently triggers the phosphorylation of Bad, resulting in neuroprotection against focal cerebral I/R injury [ 7 ]. Considerable cross-talk and interaction occur between ERK1/2 and p38 MAPK signaling pathways in response to mitogenic or stress stimuli [ 9 , 37 , 38 ]. Lian et al (1999) demonstrated that a pharmacologic inhibitor of p38 MAPK signaling effectively blocks the activation of ERK1/2 and p90RSK in stimulated neutrophils, indicating a close interaction between p90RSK and p38 MAPK signaling [ 11 ].…”

“…ERK1/2 activation directly phosphorylates 90 kDa ribosomal S6 kinase (p90RSK), which subsequently phosphorylates the pro-apoptotic protein Bad, resulting in protection against apoptosis in rat models of transient focal cerebral ischemia [ 7 , 8 ]. Previous studies have suggested that p90RSK might also play a crucial role in the crosstalk between ERK1/2 and p38 MAPK signaling pathways in in vitro [ 9 ] and in vivo [ 10 ] models. Lian et al (1999) showed that the p38 MAPK inhibitor SB203580, at higher concentrations, inhibits the activation of ERK1/2 and p90RSK in stimulated neutrophils, indicating a close relationship between p38 MAPK and p90RSK signaling cascades [ 11 ].…”

Delphinidin induces antiproliferation and apoptosis of endometrial cells by regulating cytosolic calcium levels and mitochondrial membrane potential depolarization

“…41 Also, the leptin present in the peritoneal fluid of patients with endometriosis activates the JAK2/STAT3 pathway and induces ERK1/2, which stimulates the growth of endometrial cells during endometriosis. 45 Furthermore, the anthocyanin malvidin is known to increase the activity of P38, while decreasing the activity of ERK1/2. Additionally, delphinidin and U0126 were found to have a synergic antiproliferative effect in the VK2/E6E7 and End1/E6E7 cell lines.…”

“…The tissuetype plasminogen activator induces the serial activation of ERK1/2, P90RSK, and P38, and promotes the survival of the M1 macrophages in injured kidneys. 45 Furthermore, the anthocyanin malvidin is known to increase the activity of P38, while decreasing the activity of ERK1/2. 46 Similarly, our results demonstrated that delphinidin increased the phosphor-P90RSK and P38 MAPK but not that of EKR1/2.…”