Activation and Clinical Significance of p38 MAPK Signaling Pathway in Patients With Severe Trauma

Wang, Yi Xin; Xu, Xinjian; Su, Wan‐Fu; Wang, Qiang; Zhu, Wenxu; Chen, Fen; Ge, Jian; Liu, Yu Jian; Li, Yi Dong; Sun, Yan; Gao, Wen Chao; Ruan, Can Ping

doi:10.1016/j.jss.2008.10.030

Cited by 18 publications

(13 citation statements)

References 23 publications

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“…This is consistent with previous studies showing elevated IL-6 levels in trauma patients [23;24]. The lack of a measurable IL-1β, TNFα or IL-10 in the plasma may be inpart due to the time of sample collection, which was approximately 1 week post-injury.…”

Section: Discussionsupporting

confidence: 92%

Toll-like receptor responses are suppressed in trauma ICU patients

Holloway

Nicholson

Rani

et al. 2016

Journal of Surgical Research

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Background Inflammation and activation of the innate immune system is often associated with traumatic injury and may involve alterations in Toll-like receptor (TLR)-mediated responses. Methods A prospective observational study was designed and conducted. Twenty-one severely injured (ISS = 16-41) trauma ICU patients and 6 healthy volunteers that served as controls were enrolled. Anticoagulated whole blood was collected at 2-12 days after ICU admission and incubated in the presence of media alone (baseline), zymosan (TLR2 agonist) or LPS (TLR4 agonist) for 3 hrs. Supernatant levels of inflammatory cytokines (IL-1β, -6, -10, TNFα) were determined. Results TLR2 and TLR4-mediated activation of whole blood cell cultures from both healthy volunteers and subjects induced elevated cytokine levels over that observed in unstimulated cultures. Baseline values of IL-6 were significantly elevated in subject cultures as compared to healthy volunteers. Healthy volunteer cultures had 2-3-fold greater levels of IL-6 and TNFα than subject cultures when stimulated with zymosan (TLR2 agonist) or LPS (TLR4 agonist). IL-1β and IL-10 levels did not differ significantly between healthy volunteers and subjects. Conclusions The ability of circulating leukocytes from trauma ICU patients to be activated by TLR agonists is markedly suppressed and may play a role in the development of subsequent infectious complications.

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Section: Discussionsupporting

confidence: 92%

Toll-like receptor responses are suppressed in trauma ICU patients

Holloway

Nicholson

Rani

et al. 2016

Journal of Surgical Research

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“…Increased activity of CD73 (5=-ectonucleotidase), the main regulator of adenosine metabolism, has been documented in exercising rats (38). We and others have shown that adenosine receptor expression can rapidly be increased in the presence of adenosine itself or stress induced by the addition of lipopolysaccharide (16,17,53,76,80). This is the first report showing that adenosine receptors are upregulated by continuous exercise.…”

Section: Adenosine Receptors Are Upregulated By Exercise: a Potentialmentioning

confidence: 71%

Exercise attenuates inflammation and limits scar thinning after myocardial infarction in mice

Puhl

Müller

Wagner

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Although exercise mediates beneficial effects in patients after myocardial infarction (MI), the underlying mechanisms as well as the question of whether an early start of exercise after MI is safe or even beneficial are incompletely resolved. The present study analyzed the effects of exercise before and reinitiated early after MI on cardiac remodeling and function. Male C57BL/6N mice were housed sedentary or with the opportunity to voluntarily exercise for 6 wk before MI induction (ligation of the left anterior descending coronary artery) or sham operation. After a 5-day exercise-free phase after MI, mice were allowed to reexercise for another 4 wk. Exercise before MI induced adaptive hypertrophy with moderate increases in heart weight, cardiomyocyte diameter, and left ventricular (LV) end-diastolic volume, but without fibrosis. In sedentary mice, MI induced eccentric LV hypertrophy with massive fibrosis but maintained systolic LV function. While in exercised mice gross LV end-diastolic volumes and systolic function did not differ from sedentary mice after MI, LV collagen content and thinning of the infarcted area were reduced. This was associated with ameliorated activation of inflammation, mediated by TNF-␣, IL-1␤, and IL-6, as well as reduced activation of matrix metalloproteinase 9. In contrast, no differences in the activation patterns of various MAPKs or adenosine receptor expressions were observed 5 wk after MI in sedentary or exercised mice. In conclusion, continuous exercise training before and with an early reonset after MI ameliorates adverse LV remodeling by attenuating inflammation, fibrosis, and scar thinning. Therefore, an early reonset of exercise after MI can be encouraged. exercise; remodeling; scar thinning; magnetic resonance imaging; fibrosis; myocardial infarction NEW & NOTEWORTHY Our data provide new insights into the exercise-mediated cardioprotection by implying that an early reinitiation of exercise after myocardial infarction attenuates left ventricular fibrosis and scar thinning, presumably by attenuating the coordinated proinflammatory response involving TNF-␣, IL-6, and IL-1␤. These findings could translate into clinical benefits in patients.CORONARY ARTERY DISEASE is the single most frequent cause of death worldwide. In Europe, every sixth man and every seventh woman will die of myocardial infarction (MI) (71). Those patients who survive MI frequently develop systolic heart failure due to the infarct-induced loss of functional myocardium per se and remodeling of the remainder of the left ventricular (LV) myocardium, which is frequently associated with thinning of the LV wall in the area of MI and its border zone, LV dilation, and systolic dysfunction. These parameters of myocardial remodeling are important prognostic markers for the long-term outcome of these patients. For instance, regional wall thinning is associated with postinfarction ventricular arrhythmia (36) and adverse outcome in patients undergoing coronary artery bypass surgery (87).Scar formation occurs secondary to isc...

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“…However, numerous studies have determined that p38 MAPK may be correlated with apoptosis in various cancer cells (35). The p38 MAPK can regulate cell proliferation and apoptosis through phosphorylation of p53, increased c-myc expression and regulation of Fas/FasL-mediated apoptosis (36). The impact of p38 MAPK on cell cycle regulators plays a crucial role in oncogene-induced senescence involved in the suppression of tumorigenesis and replicative senescence (18).…”

Section: Discussionmentioning

confidence: 99%

The effects of fucodian on senescence are controlled by the p16INK4a-pRb and p14Arf-p53 pathways in hepatocellular carcinoma and hepatic cell lines

Min

Kim

Lee

et al. 2014

International Journal of Oncology

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Fucoidan is known to have various pharmacological effects, including antitumor activity. Although it has potential as a therapeutic agent for cancer cells, the anti-senescence effects and detailed mechanism of action remain poorly understood in normal hepatic cells. We investigated the anticancer functions of fucoidan using HepG2 cells as well as the mechanisms mediating the anti-senescent actions in Chang liver cells. Fucoidan effectively inhibited HepG2 cell viability and induced apoptosis. Also, fucoidan-induced G1 phase arrest was caused by the activity of the p16INK4a-Rb and p14Arf-p53 pathways. Furthermore, upregulation of p16INK4a was critical to the antitumor activity of HepG2 cells treated with fucoidan and was correlated with inhibition of Cdk4 and pRb and upregulation of p21 expression. Our results suggest that fucoidan upregulates INK4a locus genes to induce apoptosis through p38 MAPK in HepG2 cells. Moreover, it prevents cellular senescence of Chang-L cells, by decreasing p14Arf expression as cells enter quiescence, with the reduction of p16INK4a. Fucoidan treatment also downregulated the expression of α2M. In conclusion, fucoidan can be considered a potential therapeutic agent against liver cancer that does not cause senescence in normal hepatic cells. Thus, it may be possible to use fucoidan therapeutically in both tumor suppression and aging.

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Activation and Clinical Significance of p38 MAPK Signaling Pathway in Patients With Severe Trauma

Cited by 18 publications

References 23 publications

Toll-like receptor responses are suppressed in trauma ICU patients

Toll-like receptor responses are suppressed in trauma ICU patients

Exercise attenuates inflammation and limits scar thinning after myocardial infarction in mice

The effects of fucodian on senescence are controlled by the p16INK4a-pRb and p14Arf-p53 pathways in hepatocellular carcinoma and hepatic cell lines

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