p38 MAP-kinase inhibitor protects against platelet-activating factor-induced death in mice

Abhilasha, Kandahalli Venkataranganayaka; Sumanth, Mosale Seetharam; Chaithra, Vyala Hanumanthareddy; Jacob, Shancy Petsel; Thyagarajan, Anita; Sahu, Ravi P.; Rajesh, R.; Prabhu, K. Sandeep; Kemparaju, K.; Travers, Jeffrey B.; Chen, Chu Huang; Marathe, Gopal K.

doi:10.1016/j.freeradbiomed.2019.08.019

Cited by 21 publications

(19 citation statements)

References 70 publications

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“…The mitogen-activated protein kinase (MAPK)/p38 signaling pathway is well known to exert a crucial role in balancing cell survival and cell death [9][10][11]. Inhibition of the MAPK/p38 signaling pathway is known to suppress cell apoptosis and the expression of pro-inflammatory cytokines in related cells [12,13]. Related studies report that targeting the VEGF/HIP-1/p38 signaling pathway can regulate pathophysiological angiogenesis and tissue repair [14,15].…”

Section: Introductionmentioning

confidence: 99%

p38 promoted retinal micro-angiogenesis through up-regulated RUNX1 expression in diabetic retinopathy

et al. 2020

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Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and is characterized by visible microvascular alterations including retinal ischemia–reperfusion injury, inflammation, abnormal permeability, neovascularization and macular edema. Despite the available treatments, some patients present late in the course of the disease when treatment is more difficult. Hence, it is crucial that the new targets are found and utilized in the clinical therapy of DR. In the present study, we constructed a DR animal model and a model in HRMECs to investigate the relationship between p38 and RUNX1 in retinal micro-angiogenesis in diabetic retinopathy. We found that p38 could promote retinal micro-angiogenesis by up-regulating RUNX1 expression in diabetic retinopathy. This suggested that the p38/ RUNX1 pathway could become a new retinal micro-angiogenesis target in DR treatment.

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Section: Introductionmentioning

confidence: 99%

p38 promoted retinal micro-angiogenesis through up-regulated RUNX1 expression in diabetic retinopathy

et al. 2020

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“…The P38 protein functions by double phosphorylating the serine and threonine of the tripeptide domain TGY. SB203580 is a specific inhibitor of the P38 protein phosphorylation with extremely low immunotoxicity to the body and is widely used in P38 functional studies (Abhilasha et al, 2019). In this study, no significant change was found in the P38 gene expression between the SB203580 + LPS and LPS groups.…”

Section: Discussionmentioning

confidence: 53%

PtP38 May Increase the Immune Ability of Portunus trituberculatus Stimulated by LPS Imitating a Gram-Negative Bacterial Infection

Wei

Zhu

et al. 2021

Front. Mar. Sci.

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The P38 mitogen-activated protein kinase (MAPK) signal transduction pathway is widespread in organisms and plays important roles in immune activities. The infection mechanism of environmental gram-negative bacteria on crustaceans is an important scientific problem. In this study, the cDNA full-length sequence of Portunus trituberculatus P38 (PtP38) was cloned and its structure was analyzed by bioinformatics methods. To study the function of the PtP38 gene after a Gram-negative bacterial infection, we injected P. trituberculatus with LPS to activate the immune response instead of directly infecting with Gram-negative bacteria. With LPS stimulation, the expression of the PtP38 gene in different tissues increased significantly. At the same time, the expression of immune-related genes (ALF and crustin) in the hepatopancreas, activities of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and inducible nitric oxide synthase (iNOS) enzymes], and expression of apoptosis-related genes (caspase2 and caspase3) were increased significantly. To further conform the function of PtP38 in the immune response, we injected P. trituberculatus with P38 inhibitor and subsequently injected with LPS. The results showed that the expression of immune-related genes was inhibited, the activity of antioxidant enzymes was decreased, and the expression of apoptosis-related genes were inhibited. Thus, we speculated that PtP38 may increase the immune ability by improving the expression of antimicrobial peptides, increasing the activity of oxidative stress-related enzymes, and promoting cell apoptosis in infected P. trituberculatus. This study also laid the foundation for further study of the P38 MAPK signaling pathway and immune mechanism of P. trituberculatus.

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“…However, only a few studies have reported that AGP-1 can induce Ca 2+ spiking in the neutrophils 32,8,7 . We found that sAGP-1 activates the MAPK pathway similar to that of PAF 33 However, the action of Siglec 5 receptor signaling is still debated as it displays both activating as well as inhibitory inflammatory signaling in neutrophils 32,[34][35][36] . Moreover, in our previous study, we have shown that sAGP-1 increases intracellular cAMP levels in platelets 7 .…”

Section: Discussionmentioning

confidence: 76%

Effect of Acute Phase Protein, Alpha – 1 – Acid Glycoprotein (AGP-1), On Platelet-Activating Factor (PAF) – Induced Pro-Inflammatory Responses

Seetharam¹,

Gopal²

2020

Int J Pharma Bio Sci

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Alpha-1-acid glycoprotein (AGP-1), an acute phase protein with ill defined functions, circulates in blood (sAGP-1) at basal levels, but levels can go up several fold upon inflammatory stimuli. Very recently, AGP-1 is shown to play a critical role in the inflammatory process by interacting with inflammatory molecules and/ or cells of the immune system. However, the interactions of sAGP-1 with endogenous inflammatory lipid mediators like Platelet-activating factor (PAF) are not well characterized. PAF is a potent autocoid with implications in several inflammatory disorders and is known to activate various cells of the innate immune system. To address this issue, we looked into the effect of sAGP-1 in PAF-induced sudden death models using Swiss Wistar (albino) mice established previously in our laboratory, to find sAGP-1 neither augmented nor inhibited the lethality of PAF in vivo. To dissect the mechanism behind this, we employed primary immune cell type namely, human neutrophils. We found that both sAGP-1 and PAF are potent activators of neutrophil adhesion and in fact, sAGP-1 even augmented PAF-induced neutrophil adhesion. Although sAGP-1 is a potent activator of neutrophils, for some responses such as PAF-induced NETosis, sAGP-1 was without any effect. These results shed light on the pro-inflammatory actions of sAGP-1 and its implications in some of the hyper-inflammatory disorders where involvement of PAF is also suspected.

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p38 MAP-kinase inhibitor protects against platelet-activating factor-induced death in mice

Cited by 21 publications

References 70 publications

p38 promoted retinal micro-angiogenesis through up-regulated RUNX1 expression in diabetic retinopathy

p38 promoted retinal micro-angiogenesis through up-regulated RUNX1 expression in diabetic retinopathy

PtP38 May Increase the Immune Ability of Portunus trituberculatus Stimulated by LPS Imitating a Gram-Negative Bacterial Infection

Effect of Acute Phase Protein, Alpha – 1 – Acid Glycoprotein (AGP-1), On Platelet-Activating Factor (PAF) – Induced Pro-Inflammatory Responses

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