Pro- and anti-inflammatory responses are regulated simultaneously from the first moments of septic shock

2011 ◽  
Vol 22 (2) ◽  
pp. 82-87 ◽  
Author(s):  
Eduardo Tamayo ◽  
Ana Fernández ◽  
Raquel Almansa ◽  
Elena Carrasco ◽  
María Heredia ◽  
...  
Keyword(s):  
Septic Shock ◽  
Inflammatory Responses ◽  
Anti Inflammatory

scholarly journals Antiseptic Effect of Ps-K18: Mechanism of Its Antibacterial and Anti-Inflammatory Activities

2019 ◽  
Vol 20 (19) ◽  
pp. 4895 ◽  
Author(s):  
Mihee Jang ◽  
Jieun Kim ◽  
Yujin Choi ◽  
JeongKyu Bang ◽  
Yangmee Kim
Keyword(s):  
Septic Shock ◽  
Antibacterial Activity ◽  
Bioactive Peptides ◽  
Liver Toxicity ◽  
Inflammatory Responses ◽  
Lung Damage ◽  
Peptide Antibiotic ◽  
Gram Negative ◽  
Innate Defense ◽  
Anti Inflammatory

Recently, bioactive peptides have attracted attention for their therapeutic applications in the pharmaceutical industry. Among them, antimicrobial peptides are candidates for new antibiotic drugs. Since pseudin-2 (Ps), isolated from the skin of the paradoxical frog Pseudis paradoxa, shows broad-spectrum antibacterial activity with high cytotoxicity, we previously designed Ps-K18 with a Lys substitution for Leu18 in Ps, which showed high antibacterial activity and low toxicity. Here, we examined the potency of Ps-K18, aiming to develop antibiotics derived from bioactive peptides for the treatment of Gram-negative sepsis. We first investigated the antibacterial mechanism of Ps-K18 based on confocal micrographs and field emission scanning electron microscopy, confirming that Ps-K18 targets the bacterial membrane. Anti-inflammatory mechanism of Ps-K18 was investigated by secreted alkaline phosphatase reporter gene assays and RT-PCR, which revealed that Ps-K18 activates innate defense via Toll-like receptor 4-mediated nuclear factor-kappa B signaling pathways. Moreover, we investigated the antiseptic effect of Ps-K18 using a lipopolysaccharide or Escherichia coli K1-induced septic shock mouse model. Ps-K18 significantly reduced bacterial growth and inflammatory responses in the septic shock model. Ps-K18 showed low renal and liver toxicity and attenuated lung damage effectively. This study suggests that Ps-K18 is a potent peptide antibiotic that could be applied therapeutically to Gram-negative sepsis.

scholarly journals Implications of Statin Use on Vasopressor Therapy in the Setting of Septic Shock

2018 ◽  
Vol 53 (3) ◽  
pp. 152-156
Author(s):  
Chelsey M. McPheeters ◽  
Jennifer A. Wiedmar ◽  
Christina M. Pinkston ◽  
Kyle A. Weant
Keyword(s):  
Septic Shock ◽  
Inflammatory Responses ◽  
Control Group ◽  
Vasopressor Therapy ◽  
Statin Group ◽  
Improved Outcomes ◽  
Anti Inflammatory ◽  
Time Of Admission ◽  
Statin Use

Background: Pleiotropic anti-inflammatory and immunomodulatory effects of statins have been associated with improved outcomes in the critically ill population. Objective: To evaluate the implications of prior statin use on the duration of vasopressor therapy in the setting of septic shock. Methods: This was a retrospective, multicenter study of adult patients who were diagnosed with septic shock. Patients were included if they were treated with any vasopressor for greater than 6 hours from the time of admission. The primary outcome was to compare the duration of vasopressor therapy in patients with septic shock with and without previous statin exposure. Results: A total of 88 statin-exposed cases and 205 unexposed controls were included in the analysis. Despite 92% of statin-exposed patients being reinitiated on therapy within 24 hours, the duration of vasopressors did not differ between groups (44 hours, statin group vs 53 hours, control group, P = .51). There were also no mortality differences between the statin group and the controls (40% vs 47%, P = .27). Conclusions: Long-term statin exposure does not impact the duration of vasopressor therapy in septic shock. The lack of differences in clinical outcomes supports the concept that sepsis involves pro- and anti-inflammatory pathways as well as other nonimmunologic pathways. Results lend further credence to the recent conceptualization of sepsis, with complications leading to organ dysfunction caused not primarily due to inflammatory responses but by a dysregulated response to infection.

scholarly journals Flavonoids: Nutraceuticals for Rheumatic Diseases via Targeting of Inflammasome Activation

2021 ◽  
Vol 22 (2) ◽  
pp. 488
Author(s):  
Young-Su Yi
Keyword(s):  
Rheumatic Diseases ◽  
Fruits And Vegetables ◽  
Inflammatory Responses ◽  
Protein Complexes ◽  
Cellular Damage ◽  
Inflammatory Rheumatic Diseases ◽  
Inflammasome Activation ◽  
Central Feature ◽  
Inflammatory Protein ◽  
Anti Inflammatory

Inflammation, an innate immune response that prevents cellular damage caused by pathogens, consists of two successive mechanisms, namely priming and triggering. While priming is an inflammation-preparation step, triggering is an inflammation-activation step, and the central feature of triggering is the activation of inflammasomes and intracellular inflammatory protein complexes. Flavonoids are natural phenolic compounds predominantly present in plants, fruits, and vegetables and are known to possess strong anti-inflammatory activities. The anti-inflammatory activity of flavonoids has long been demonstrated, with the main focus on the priming mechanisms, while increasing numbers of recent studies have redirected the research focus on the triggering step, and studies have reported that flavonoids inhibit inflammatory responses and diseases by targeting inflammasome activation. Rheumatic diseases are systemic inflammatory and autoimmune diseases that primarily affect joints and connective tissues, and they are associated with numerous deleterious effects. Here, we discuss the emerging literature on the ameliorative role of flavonoids targeting inflammasome activation in inflammatory rheumatic diseases.

scholarly journals Administration route governs the therapeutic efficacy, biodistribution and macrophage targeting of anti-inflammatory nanoparticles in the lung

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lu Wang ◽  
Yafei Rao ◽  
Xiali Liu ◽  
Liya Sun ◽  
Jiameng Gong ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Lung Inflammation ◽  
Respiratory Diseases ◽  
Inflammatory Responses ◽  
The Other ◽  
Target Cells ◽  
Administration Route ◽  
Toll Like Receptor ◽  
Administration Routes ◽  
Anti Inflammatory

Abstract Background Uncontrolled inflammation is a central problem for many respiratory diseases. The development of potent, targeted anti-inflammatory therapies to reduce lung inflammation and re-establish the homeostasis in the respiratory tract is still a challenge. Previously, we developed a unique anti-inflammatory nanodrug, P12 (made of hexapeptides and gold nanoparticles), which can attenuate Toll-like receptor-mediated inflammatory responses in macrophages. However, the effect of the administration route on its therapeutic efficacy and tissue distribution remained to be defined. Results In this study, we systematically compared the effects of three different administration routes [the intratracheal (i.t.), intravenous (i.v.) and intraperitoneal (i.p.)] on the therapeutic activity, biodistribution and pulmonary cell targeting features of P12. Using the LPS-induced ALI mouse model, we found that the local administration route via i.t. instillation was superior in reducing lung inflammation than the other two routes even treated with a lower concentration of P12. Further studies on nanoparticle biodistribution showed that the i.t. administration led to more accumulation of P12 in the lungs but less in the liver and other organs; however, the i.v. and i.p. administration resulted in more nanoparticle accumulation in the liver and lymph nodes, respectively, but less in the lungs. Such a lung favorable distribution was also determined by the unique surface chemistry of P12. Furthermore, the inflammatory condition in the lung could decrease the accumulation of nanoparticles in the lung and liver, while increasing their distribution in the spleen and heart. Interestingly, the i.t. administration route helped the nanoparticles specifically target the lung macrophages, whereas the other two administration routes did not. Conclusion The i.t. administration is better for treating ALI using nanodevices as it enhances the bioavailability and efficacy of the nanodrugs in the target cells of the lung and reduces the potential systematic side effects.

scholarly journals Luteolin transforms the polarity of bone marrow-derived macrophages to regulate the cytokine storm

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Shuxia Wang ◽  
Shuhang Xu ◽  
Jing Zhou ◽  
Li Zhang ◽  
Xiaodong Mao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Inflammatory Responses ◽  
Bone Marrow Cells ◽  
Membrane Surface ◽  
Inflammatory Factors ◽  
Mouse Bone Marrow ◽  
Macrophage Polarisation ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
M1 Type

Abstract Background Macrophages are indispensable regulators of inflammatory responses. Macrophage polarisation and their secreted inflammatory factors have an association with the outcome of inflammation. Luteolin, a flavonoid abundant in plants, has anti-inflammatory activity, but whether luteolin can manipulate M1/M2 polarisation of bone marrow-derived macrophages (BMDMs) to suppress inflammation is still unclear. This study aimed to observe the effects of luteolin on the polarity of BMDMs derived from C57BL/6 mice and the expression of inflammatory factors, to explore the mechanism by which luteolin regulates the BMDM polarity. Methods M1-polarised BMDMs were induced by lipopolysaccharide (LPS) + interferon (IFN)-γ and M2-polarisation were stimulated with interleukin (IL)-4. BMDM morphology and phagocytosis were observed by laser confocal microscopy; levels of BMDM differentiation and cluster of differentiation (CD)11c or CD206 on the membrane surface were assessed by flow cytometry (FCM); mRNA and protein levels of M1/M2-type inflammatory factors were performed by qPCR and ELISA, respectively; and the expression of p-STAT1 and p-STAT6 protein pathways was detected by Western-blotting. Results The isolated mouse bone marrow cells were successfully differentiated into BMDMs, LPS + IFN-γ induced BMDM M1-phenotype polarisation, and IL-4 induced M2-phenotype polarisation. After M1-polarised BMDMs were treated with luteolin, the phagocytosis of M1-polarized BMDMs was reduced, and the M1-type pro-inflammatory factors including IL-6, tumour necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), and CD86 were downregulated while the M2-type anti-inflammatory factors including IL-10, IL-13, found in inflammatory zone (FIZZ)1, Arginase (Arg)1 and CD206 were upregulated. Additionally, the expression of M1-type surface marker CD11c decreased. Nevertheless, the M2-type marker CD206 increased; and the levels of inflammatory signalling proteins phosphorylated signal transducer and activator of transcription (p-STAT)1 and p-STAT6 were attenuated and enhanced, respectively. Conclusions Our study suggests that luteolin may transform BMDM polarity through p-STAT1/6 to regulate the expression of inflammatory mediators, thereby inhibiting inflammation. Naturally occurring luteolin holds promise as an anti-inflammatory and immunomodulatory agent.

scholarly journals Platonin, a Cyanine Photosensitizing Dye, Ameliorates Inflammatory Responses in Vascular Smooth Muscle Cells by Modulating Inflammatory Transcription Factors

2021 ◽  
Vol 11 (3) ◽  
pp. 1130
Author(s):  
Chih-Wei Chiu ◽  
Chih-Hao Yang ◽  
Jie-Heng Tsai ◽  
Cheng-Ying Hsieh ◽  
Shih-Yi Huang
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Inflammatory Responses ◽  
Muscle Cells ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Ifn Γ ◽  
Anti Inflammatory

Inflammation of the arterial wall is critical to atherosclerosis pathogenesis. The switch of vascular smooth muscle cells (VSMCs) to macrophage-like cells is essential in the exacerbation of vascular inflammation. Platonin, a cyanine photosensitizing dye, exhibits protective effects in sepsis, trauma, and acute ischemic stroke through its anti-inflammatory capacity in macrophages. The present study investigated the effects and underlying mechanisms of platonin in inflammatory VSMCs. Pretreatment with platonin suppressed the expression of inducible nitric oxide synthetase and mature interleukin-1β but not that of monocyte chemoattractant protein-1 (MCP-1) in VSMCs stimulated by a combination of lipopolysaccharide and interferon-γ (LPS/IFN-γ). Furthermore, platonin inhibited LPS/IFN-γ-induced Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation though the direct reduction of p65Ser536 phosphorylation but not the restoration of Inhibitor of nuclear factor kappa B (IκBα) degradation in VSMCs. However, platonin inhibited Oxidized low-density lipoprotein (ox-LDL)-induced MCP-1 production, possibly through the attenuation of Activator protein 1 (AP-1) binding activity and C-Jun N-terminal kinases ½ (JNK1/2) phosphorylation. Platonin also lowered lipid drop accumulation in VSMCs in Oil red O staining assay. The results collectively indicated that platonin has a vascular protective property with potent anti-inflammatory effects in VSMCs. In conclusion, platonin should be a potential for treating vascular inflammatory diseases such as atherosclerosis.

scholarly journals Skin Immunomodulation during Regeneration: Emerging New Targets

2021 ◽  
Vol 11 (2) ◽  
pp. 85
Author(s):  
Loubna Mazini ◽  
Luc Rochette ◽  
Yousra Hamdan ◽  
Gabriel Malka
Keyword(s):  
Cell Proliferation ◽  
Tissue Repair ◽  
Inflammatory Responses ◽  
Skin Barrier ◽  
Adipose Derived Stem Cells ◽  
T And B Cells ◽  
Tumor Growth Factor ◽  
Anti Inflammatory ◽  
Skin Function ◽  
Epidermal Regeneration

Adipose-Derived Stem Cells (ADSC) are present within the hypodermis and are also expected to play a pivotal role in wound healing, immunomodulation, and rejuvenation activities. They orchestrate, through their exosome, the mechanisms associated to cell differentiation, proliferation, and cell migration by upregulating genes implicated in different functions including skin barrier, immunomodulation, cell proliferation, and epidermal regeneration. ADSCs directly interact with their microenvironment and specifically the immune cells, including macrophages and T and B cells, resulting in differential inflammatory and anti-inflammatory mechanisms impacting, in return, ADSCs microenvironment and thus skin function. These useful features of ADSCs are involved in tissue repair, where the required cell proliferation, angiogenesis, and anti-inflammatory responses should occur rapidly in damaged sites. Different pathways involved have been reported such as Growth Differentiation Factor-11 (GDF11), Tumor Growth Factor (TGF)-β, Metalloproteinase (MMP), microRNA, and inflammatory cytokines that might serve as specific biomarkers of their immunomodulating capacity. In this review, we try to highlight ADSCs’ network and explore the potential indicators of their immunomodulatory effect in skin regeneration and aging. Assessment of these biomarkers might be useful and should be considered when designing new clinical therapies using ADSCs or their specific exosomes focusing on their immunomodulation activity.

scholarly journals In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and in Vivo Analysis of Its Therapeutic Potential in Osteoarthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 615
Author(s):  
Shang-En Huang ◽  
Erna Sulistyowati ◽  
Yu-Ying Chao ◽  
Bin-Nan Wu ◽  
Zen-Kong Dai ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Serum Levels ◽  
Gene Expressions ◽  
Tnf Α ◽  
Anti Inflammatory

Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA.

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