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Electric Stimulation Hyperthermia Relieves Inflammation via the Suppressor of Cytokine Signaling 3-Toll Like Receptor 4 Pathway in a Prostatitis Rat Model.

ABSTRACT: PURPOSE:Chronic prostatitis (CP), including chronic pelvic pain syndrome (CPPS), is the most commonly encountered manifestation of prostatitis. The aim of this study was to evaluate the effect of electric stimulation hyperthermia treatment (ESHT) on CP/CPPS and to explore the underlying mechanism. MATERIALS AND METHODS:RWPE-2 cells with lipopolysaccharide-induced inflammation and a prostatitis rat model induced by 17?-estradiol and dihydrotestosterone underwent sham, electric stimulation, or ESHT treatment. Four weeks later, cells, supernatants, and rat prostates were collected for analysis using immunohistochemistry, Western blots, and enzyme-linked immunosorbent assays. RESULTS:We found that ESHT improved prostatitis in vivo and attenuated inflammation in vitro. ESHT significantly induced suppressor of cytokine signaling 3 (SOCS3) expression and subsequently promoted HSP70. It attenuated inflammation through decreased expression of toll-like receptor 4 (TLR4), nuclear factor kappa B, and subsequent inflammatory cytokines. ESHT also inhibited apoptosis and released growth factor in tissue affected by prostatitis. CONCLUSIONS:ESHT improved CP/CPPS and reversed pathologic changes of prostatitis by inhibiting the SOCS3-TLR4 pathway.

SUBMITTER: Zhu GQ

PROVIDER: S-EPMC7308236 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Electric Stimulation Hyperthermia Relieves Inflammation <i>via</i> the Suppressor of Cytokine Signaling 3-Toll Like Receptor 4 Pathway in a Prostatitis Rat Model.

Zhu Guan Qun GQ Jeon Seung Hwan SH Lee Kyu Won KW Tian Wen Jie WJ Cho Hyuk Jin HJ Ha U Syn US Hong Sung Hoo SH Lee Ji Youl JY Moon Myeong Keon MK Moon Sung Hee SH Kim Sae Woong SW Bae Woong Jin WJ

The world journal of men's health 20190723 3

<h4>Purpose</h4>Chronic prostatitis (CP), including chronic pelvic pain syndrome (CPPS), is the most commonly encountered manifestation of prostatitis. The aim of this study was to evaluate the effect of electric stimulation hyperthermia treatment (ESHT) on CP/CPPS and to explore the underlying mechanism.<h4>Materials and methods</h4>RWPE-2 cells with lipopolysaccharide-induced inflammation and a prostatitis rat model induced by 17β-estradiol and dihydrotestosterone underwent sham, electric stim ...[more]

PMID: 31385476

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Project description:BACKGROUND:This study aimed to evaluate effects of electric vagal nerve stimulation on early postoperation cognitive dysfunction in aged rats. METHODS:A total of 33 male Sprague Dawley rats were selected and assigned randomly to three groups, control group (C, n?=?10), splenectomy group (S, n?=?10) and splenectomy+vagal nerve stimulation group (SV, n?=?13). Behavior and memory of rats were evaluated by Open Field Test and Morris Water Maze. Levels of TNF-?, IL-6 and IL-10 in serum were measured by ELISA. The level of TNF-? protein in hippocampus was assessed by Western blotting. rt-PCR was used to detect mRNA expression of NF-?B in hippocampus. RESULTS:During anesthesia/operation, vital life signs of rats were stable. In SV group, vagal nerve stimulation decreased heart rate lower than 10% of basic level and kept it at a stable range by regulating stimulation intensity. After stimulation stop, heart rate returned to the basic level again. This indicated that the model of vagal nerve stimulation was successful. Serum levels of TNF-? and IL-6 increased by the operation/anesthesia, but they decreased with vagal nerve stimulation (all P?<?0.05). TNF-? protein and mRNA expression of NF-?B in hippocampus were also eliminated by vagal nerve stimulation compared to S group (P?<?0.05). Results of Morris Water Maze showed escape latency of postoperation in S group was significantly longer than C group (P?<?0.05), and times of crossing platform in S group was lower than that of C group (P?<?0.05). Although escape latency of postopration in SV group was shorter than that of S group, there was no significant difference between two groups. Meanwhile there were no significant differences of behavior test in Open Field test between three groups, although vagal nerve stimulation improved partly active explore behavior compared to S group. CONCLUSION:The inflammation caused by operation and general anesthesia was an important reason of early postoperation cognitive dysfunction, and electric vagal nerve stimulation could inhibit the inflammation. Meanwhile, vagal nerve stimulation could ameliorate early postoperation cognitive dysfunction partly, but its protective effects were not enough and should be studied and improved in future.

Project description:Rapid determination of an infective aetiology causing neurological inflammation in the cerebrospinal fluid can be challenging in clinical practice. Post-surgical nosocomial infection is difficult to diagnose accurately, as it occurs on a background of altered cerebrospinal fluid composition due to the underlying pathologies and surgical procedures involved. There is additional diagnostic difficulty after external ventricular drain or ventriculoperitoneal shunt surgery, as infection is often caused by pathogens growing as biofilms, which may fail to elicit a significant inflammatory response and are challenging to identify by microbiological culture. Despite much research effort, a single sensitive and specific cerebrospinal fluid biomarker has yet to be defined which reliably distinguishes infective from non-infective inflammation. As a result, many patients with suspected infection are treated empirically with broad-spectrum antibiotics in the absence of definitive diagnostic criteria. To begin to address these issues, we examined cerebrospinal fluid taken at the point of clinical equipoise to diagnose cerebrospinal fluid infection in 14 consecutive neurosurgical patients showing signs of inflammatory complications. Using the guidelines of the Infectious Diseases Society of America, six cases were subsequently characterized as infected and eight as sterile inflammation. Twenty-four contemporaneous patients with idiopathic intracranial hypertension or normal pressure hydrocephalus were included as non-inflamed controls. We measured 182 immune and neurological biomarkers in each sample and used pathway analysis to elucidate the biological underpinnings of any biomarker changes. Increased levels of the inflammatory cytokine interleukin-6 and interleukin-6-related mediators such as oncostatin M were excellent indicators of inflammation. However, interleukin-6 levels alone could not distinguish between bacterially infected and uninfected patients. Within the patient cohort with neurological inflammation, a pattern of raised interleukin-17, interleukin-12p40/p70 and interleukin-23 levels delineated nosocomial bacteriological infection from background neuroinflammation. Pathway analysis showed that the observed immune signatures could be explained through a common generic inflammatory response marked by interleukin-6 in both nosocomial and non-infectious inflammation, overlaid with a toll-like receptor-associated and bacterial peptidoglycan-triggered interleukin-17 pathway response that occurred exclusively during infection. This is the first demonstration of a pathway dependent cerebrospinal fluid biomarker differentiation distinguishing nosocomial infection from background neuroinflammation. It is especially relevant to the commonly encountered pathologies in clinical practice, such as subarachnoid haemorrhage and post-cranial neurosurgery. While requiring confirmation in a larger cohort, the current data indicate the potential utility of cerebrospinal fluid biomarker strategies to identify differential initiation of a common downstream interleukin-6 pathway to diagnose nosocomial infection in this challenging clinical cohort.

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Project description:Neonates rely on their innate immune system, and neutrophils in particular, to recognize and combat life-threatening bacterial infections. Pretreatment with lipopolysaccharide (LPS), a toll-like receptor (TLR) 4 agonist, improves survival to polymicrobial sepsis in neonatal mice by enhancing neutrophil recruitment. To understand the response of human neonatal neutrophils to TLR4 stimulation, ex vivo spontaneous neutrophil migration, neutrophil transcriptomics, and cytokine production in the presence and absence of LPS were measured directly from whole blood of adults, term neonates, and preterm neonates. Spontaneous neutrophil migration was measured on novel microfluidic devices with time-lapse imaging for 10 h. Genome-wide neutrophil transcriptomics and plasma cytokine concentrations were also determined. Preterm neonates had significantly fewer spontaneously migrating neutrophils at baseline, and both term and preterm neonates had decreased neutrophil velocity, compared to adults. In the presence of LPS stimulation, the number of spontaneously migrating neutrophils was reduced in preterm neonates compared to term neonates and adults. Neutrophil velocity was not significantly different among groups with LPS stimulation. Preterm neonates upregulated expression of genes associated with the recruitment and response of neutrophils following LPS stimulation, but failed to upregulate the expression of genes associated with antimicrobial and antiviral responses. Plasma levels of IL-1β, IL-6, IL-8, MIP-1α, and TNF-α increased in response to LPS stimulation in all groups, but IL-10 was increased only in term and preterm neonates. In conclusion, age-specific changes in spontaneous neutrophil migration counts are not affected by LPS despite changes in gene expression and cytokine production. KEY MESSAGES:Preterm neonates have reduced spontaneous neutrophil migration compared to term neonates and adults in the absence and presence of TLR4 stimulation. Preterm and term neonates have reduced neutrophil velocities compared to adults in the absence of TLR4 stimulation but no difference in the presence of TLR4 stimulation. Unique transcriptomic response to TLR4 stimulation is observed in neutrophils from preterm neonates, term neonates, and adults. TLR4 stimulation produces an age-specific cytokine response.

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Dataset Information

Electric Stimulation Hyperthermia Relieves Inflammation via the Suppressor of Cytokine Signaling 3-Toll Like Receptor 4 Pathway in a Prostatitis Rat Model.

Publications

Electric Stimulation Hyperthermia Relieves Inflammation <i>via</i> the Suppressor of Cytokine Signaling 3-Toll Like Receptor 4 Pathway in a Prostatitis Rat Model.

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