scholarly journals Cytokines and Chemokines in Chikungunya Virus Infection: Protection or Induction of Pathology

Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 415
Author(s):  
Chintana Chirathaworn ◽  
Jira Chansaenroj ◽  
Yong Poovorawan
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Responses ◽  
Chikungunya Virus ◽  
Inflammatory Responses ◽  
Clinical Manifestations ◽  
Joint Inflammation ◽  
Chikv Infection ◽  
Chemokine Production ◽  
Persistent Symptoms ◽  
Cytokines And Chemokines

Chikungunya virus (CHIKV) infection has been commonly detected in tropical countries. The clinical manifestations of CHIKV infection are similar to those of rheumatoid arthritis. Outbreaks of CHIKV infection in Thailand have been reported, and the inductions of various cytokines and chemokines in CHIKV patients during those outbreaks have been shown. Although immune responses in CHIKV infection have been increasingly reported, the mechanisms associated with pathology induction are still not clearly understood. This review focuses on cytokine and chemokine production in CHIKV infection, in association with the severity of joint inflammation. Several cytokines and chemokines involved in the induction or regulation of inflammatory responses were shown to associate with the severe and persistent symptoms in CHIKV infection. Further studies on the difference in immune responses observed in an autoimmune disease, rheumatoid arthritis, infectious disease, and CHIKV infection, would provide additional insights useful for proper CHIKV therapy, especially in patients with severe joint pains.

scholarly journals The Role of Src Kinase in Macrophage-Mediated Inflammatory Responses

2012 ◽  
Vol 2012 ◽  
pp. 1-18 ◽  
Author(s):  
Se Eun Byeon ◽  
Young-Su Yi ◽  
Jueun Oh ◽  
Byong Chul Yoo ◽  
Sungyoul Hong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Responses ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Src Kinase ◽  
Multiple Roles ◽  
Cellular Migration ◽  
Pharmaceutical Drugs ◽  
Tyrosine Protein Kinase

Src kinase (Src) is a tyrosine protein kinase that regulates cellular metabolism, survival, and proliferation. Many studies have shown that Src plays multiple roles in macrophage-mediated innate immunity, such as phagocytosis, the production of inflammatory cytokines/mediators, and the induction of cellular migration, which strongly implies that Src plays a pivotal role in the functional activation of macrophages. Macrophages are involved in a variety of immune responses and in inflammatory diseases including rheumatoid arthritis, atherosclerosis, diabetes, obesity, cancer, and osteoporosis. Previous studies have suggested roles for Src in macrophage-mediated inflammatory responses; however, recently, new functions for Src have been reported, implying that Src functions in macrophage-mediated inflammatory responses that have not been described. In this paper, we discuss recent studies regarding a number of these newly defined functions of Src in macrophage-mediated inflammatory responses. Moreover, we discuss the feasibility of Src as a target for the development of new pharmaceutical drugs to treat macrophage-mediated inflammatory diseases. We provide insights into recent reports regarding new functions for Src that are related to macrophage-related inflammatory responses and the development of novel Src inhibitors with strong immunosuppressive and anti-inflammatory properties, which could be applied to various macrophage-mediated inflammatory diseases.

scholarly journals Mycoplasma pneumoniae-Derived Lipopeptides Induce Acute Inflammatory Responses in the Lungs of Mice

2007 ◽  
Vol 76 (1) ◽  
pp. 270-277 ◽  
Author(s):  
Takashi Shimizu ◽  
Yutaka Kida ◽  
Koichi Kuwano
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Inflammatory Responses ◽  
Lavage Fluid ◽  
Peritoneal Macrophages ◽  
Necrosis Factor Alpha ◽  
Chemokine Production ◽  
Cytokines And Chemokines ◽  
Tnf Α ◽  
Mouse Peritoneal Macrophages

ABSTRACT The pathogenesis of Mycoplasma pneumoniae infection is considered to be in part attributable to excessive immune responses. In this study, we investigated whether synthetic lipopeptides of subunit b of F0F1-type ATPase (F0F1-ATPase), NF-κB-activating lipoprotein 1 (N-ALP1), and N-ALP2 (named FAM20, sN-ALP1, and sN-ALP2, respectively) derived from M. pneumoniae induce cytokine and chemokine production and leukocyte infiltration in vivo. Intranasal administration of FAM20 and sN-ALP2 induced infiltration of leukocyte cells and production of chemokines and cytokines in bronchoalveolar lavage fluid, but sN-ALP1 failed to do so. The activity of FAM20 was notably higher than that of sN-ALP2. FAM20 and sN-ALP2 induced tumor necrosis factor alpha (TNF-α) through Toll-like receptor 2 in mouse peritoneal macrophages. Moreover, in the range of low concentrations of lipopeptides, FAM20 showed relatively high activity of inducing TNF-α in mouse peritoneal macrophages compared to synthetic lipopeptides such as MALP-2 and FSL-1, derived from Mycoplasma fermentans and Mycoplasma salivarium, respectively. These findings indicate that the F0F1-ATPase might be a key molecule in inducing cytokines and chemokines contributing to inflammatory responses during M. pneumoniae infection in vivo.

scholarly journals A critical role for IRAK4 kinase activity in Toll-like receptor–mediated innate immunity

2007 ◽  
Vol 204 (5) ◽  
pp. 1025-1036 ◽  
Author(s):  
Tae Whan Kim ◽  
Kirk Staschke ◽  
Katarzyna Bulek ◽  
Jianhong Yao ◽  
Kristi Peters ◽  
...  
Keyword(s):  
Immune Responses ◽  
Kinase Activity ◽  
Critical Role ◽  
Nuclear Factor Κb ◽  
Type I ◽  
Toll Like Receptor ◽  
Chemokine Production ◽  
Cytokines And Chemokines ◽  
Plasmacytoid Dcs

IRAK4 is a member of IL-1 receptor (IL-1R)–associated kinase (IRAK) family and has been shown to play an essential role in Toll-like receptor (TLR)–mediated signaling. We recently generated IRAK4 kinase-inactive knock-in mice to examine the role of kinase activity of IRAK4 in TLR-mediated signaling pathways. The IRAK4 kinase–inactive knock-in mice were completely resistant to lipopolysaccharide (LPS)- and CpG-induced shock, due to impaired TLR-mediated induction of proinflammatory cytokines and chemokines. Although inactivation of IRAK4 kinase activity did not affect the levels of TLR/IL-1R–mediated nuclear factor κB activation, a reduction of LPS-, R848-, and IL-1–mediated mRNA stability contributed to the reduced cytokine and chemokine production in bone marrow–derived macrophages from IRAK4 kinase–inactive knock-in mice. Both TLR7- and TLR9-mediated type I interferon production was abolished in plasmacytoid dendritic cells isolated from IRAK4 knock-in mice. In addition, influenza virus–induced production of interferons in plasmacytoid DCs was also dependent on IRAK4 kinase activity. Collectively, our results indicate that IRAK4 kinase activity plays a critical role in TLR-dependent immune responses.

scholarly journals NF-κB Pathway as a Potential Target for Treatment of Critical Stage COVID-19 Patients

2020 ◽  
Vol 11 ◽  
Author(s):  
Ralf Kircheis ◽  
Emanuel Haasbach ◽  
Daniel Lueftenegger ◽  
Willm T. Heyken ◽  
Matthias Ocker ◽  
...  
Keyword(s):  
Immune Cell ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Synergistic Effects ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Published Data ◽  
Critical Stage ◽  
Cytokines And Chemokines ◽  
Simultaneous Inhibition

Patients infected with SARS-CoV-2 show a wide spectrum of clinical manifestations ranging from mild febrile illness and cough up to acute respiratory distress syndrome, multiple organ failure, and death. Data from patients with severe clinical manifestations compared to patients with mild symptoms indicate that highly dysregulated exuberant inflammatory responses correlate with severity of disease and lethality. Epithelial-immune cell interactions and elevated cytokine and chemokine levels, i.e. cytokine storm, seem to play a central role in severity and lethality in COVID-19. The present perspective places a central cellular pro-inflammatory signal pathway, NF-κB, in the context of recently published data for COVID-19 and provides a hypothesis for a therapeutic approach aiming at the simultaneous inhibition of whole cascades of pro-inflammatory cytokines and chemokines. The simultaneous inhibition of multiple cytokines/chemokines is expected to have much higher therapeutic potential as compared to single target approaches to prevent cascade (i.e. redundant, triggering, amplifying, and synergistic) effects of multiple induced cytokines and chemokines in critical stage COVID-19 patients.

scholarly journals The Role of Intracellular Organisms in the Pathogenesis of Inflammatory Arthritis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Animesh Singh ◽  
Sarah Karrar
Keyword(s):  
Rheumatoid Arthritis ◽  
Reactive Arthritis ◽  
Inflammatory Arthritis ◽  
Molecular Mimicry ◽  
Joint Inflammation ◽  
Joint Space ◽  
Low Grade ◽  
Infectious Episode ◽  
Persistent Symptoms

Inflammatory arthritis is a condition which is characterised by recurrent episodes of joint pain and swelling. It encompasses a spectrum of disorders ranging from rheumatoid arthritis to ankylosing spondylitis. In these conditions, for reasons that are poorly understood, the immune system raises an inflammatory response within the joint space. In some cases, autoantigens have been identified (e.g., anticitrullinated peptides in rheumatoid arthritis), but the absence of these, in the seronegative arthritides, for example, raises question as to the underlying pathogenesis. Interest has, therefore, turned to host-pathogen interactions and whether aberrant immune responses to these could explain the development of arthritis. This has been most widely studied in reactive arthritis (ReA), where an infectious episode precedes the development of the joint symptoms. In this review, we present the evidence for the role of host-bacterial interactions in the pathogenesis of joint inflammation with particular emphasis on ReA. We discuss a range of possible mechanisms including molecular mimicry, persistent low grade infections, and abnormal host responses to common bacterial causes of reactive arthritis as well as discussing some of the clinical challenges that we face in making the diagnosis and in treatment of persistent symptoms.

scholarly journals Elevated APE1/Ref-1 Levels of Synovial Fluids in Patients with Rheumatoid Arthritis: Reflection of Disease Activity

2021 ◽  
Vol 10 (22) ◽  
pp. 5324
Author(s):  
In Seol Yoo ◽  
Yu-Ran Lee ◽  
Seong Wook Kang ◽  
Jinhyun Kim ◽  
Hee-Kyoung Joo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Inflammatory Responses ◽  
Joint Destruction ◽  
Joint Inflammation ◽  
Joint Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Control ◽  
The Relationship

There is growing evidence that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) regulates inflammatory responses. Rheumatoid arthritis (RA) is an autoimmune disease, which is characterized with synovitis and joint destruction. Therefore, this study was planned to investigate the relationship between APE1/Ref-1 and RA. Serum and synovial fluid (SF) were collected from 46 patients with RA, 45 patients with osteoarthritis (OA), and 30 healthy control (HC) patients. The concentration of APE1/Ref-1 in serum or SF was measured using the sandwich enzyme-linked immunosorbent assay (ELISA). The disease activity in RA patients was measured using the 28-joint disease activity score (DAS28). The serum APE1/Ref-1 levels in RA patients were significantly increased compared to HC and OA patients (0.44 ± 0.39 ng/mL for RA group vs. 0.19 ± 0.14 ng/mL for HC group, p < 0.05 and vs. 0.19 ± 0.11 ng/mL for OA group, p < 0.05). Likewise, the APE1/Ref-1 levels of SF in RA patients were also significantly increased compared to OA patients (0.68 ± 0.30 ng/mL for RA group vs. 0.31 ± 0.12 ng/mL for OA group, p < 0.001). The APE1/Ref-1 concentration in SF of RA patients was positively correlated with DAS28. Thus, APE1/Ref-1 may reflect the joint inflammation and be associated with disease activity in RA.

scholarly journals Rewiring PBMC responses to prevent CHIKV infection-specific monocyte subset redistribution and cytokine responses

2020 ◽  
Author(s):  
José Alberto Aguilar-Briseño ◽  
Mariana Ruiz Silva ◽  
Jill Moser ◽  
Mindaugas Pauzuolis ◽  
Jolanda M. Smit ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Chronic Arthritis ◽  
Target Cells ◽  
Monocyte Subset ◽  
Chikv Infection ◽  
Peripheral Blood Mononuclear ◽  
Vitro Model

AbstractInfection with the mosquito-borne Chikungunya virus (CHIKV) causes acute or chronic arthritis in humans. Inflammatory responses mediated by monocytes, the primary target cells of CHIKV infection in the blood, are considered to play an important role in CHIKV pathogenesis. A recent study revealed that the acute phase of CHIKV infection is characterized by a monocyte-driven response, with an expansion of the intermediate monocyte (IM) subset. In this study, we adopted a previously established in vitro model of CHIKV infection in peripheral blood mononuclear cells, to elucidate the mechanism and relevance of IM expansion in CHIKV replication and associated inflammatory responses. Our data show that infectious but not replication-incompetent CHIKV increases the frequency of IM and to a lesser extent, non-classical (NM) monocytes while reducing the number of classical monocytes (CM). The increase of IM or NM frequency coincided with the activation of inflammatory response and occurred in the absence of lymphocytes implying that monocyte-derived cues are sufficient to drive this effect. Importantly, priming of monocytes with LPS prevented expansion of IM and NM but had no effect on viral replication. It did however alter CHIKV-induced cytokine signature. Taken together, our data delineate the role of IM in CHIKV infection-specific innate immune responses and provide insight for the development of therapeutic strategies that may focus on rewiring monocyte immune responses to prevent CHIKV-mediated arthralgia and arthritis.

scholarly journals NF-kappaB pathway as a potential target for treatment of critical stage COVID-19 patients

2020 ◽  
Author(s):  
Ralf Kircheis ◽  
Emanuel Haasbach ◽  
Daniel Lueftenegger ◽  
Will T. Heyken ◽  
Matthias Ocker ◽  
...  
Keyword(s):  
Immune Cell ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Published Data ◽  
Critical Stage ◽  
Cytokines And Chemokines ◽  
Simultaneous Inhibition ◽  
Nf Kappab

Abstract Patients infected with SARS-CoV-2 show a wide spectrum of clinical manifestations ranging from mild febrile illness and cough up to acute respiratory distress syndrome, multiple organ failure and death. Data from patients with severe clinical manifestations compared to patients with mild symptoms indicate that highly dysregulated exuberant inflammatory responses correlate with severity of disease and lethality. Epithelial-immune cell interactions and elevated cytokine and chemokine levels, i.e. cytokine storm, seem to play a central role in severity and lethality in COVID-19. The present perspective places a central cellular pro-inflammatory signal pathway, NF-kappaB, in the context of recently published data for COVID-19 and provides a hypothesis for a therapeutic approach aiming at the simultaneous inhibition of whole cascades of pro-inflammatory cytokines and chemokines. The simultaneous inhibition of multiple cytokines/chemokines is expected to have much higher therapeutic potential as compared to single target approaches to prevent cascade (i.e. triggering, synergistic, and redundant) effects of multiple induced cytokines and chemokines in critical stage COVID-19 patients.

scholarly journals Treatment of Chikungunya Virus (CHIKV) Using Targeted Immunotherapy

2021 ◽  
Author(s):  
Fleury Augustin Nsole Biteghe ◽  
Chalomie Nyangone Ekome Toung ◽  
Jean De La Croix Ndong ◽  
Neelakshi Mungra ◽  
Tahir B. Dar ◽  
...  
Keyword(s):  
Animal Studies ◽  
Chikungunya Virus ◽  
Clinical Manifestations ◽  
Chikv Infection ◽  
Prophylactic Efficacy ◽  
Multiple Factors ◽  
Therapeutic Benefits ◽  
Infection Dynamics ◽  
Human And Mouse ◽  
Targeted Immunotherapy

Chikungunya virus (CHIKV) is the most common mosquito-borne Alphavirus infecting humans worldwide. Up to date, there are no antiviral treatments or vaccines approved to treat or prevent CHIKV for which treatments remain symptomatic based on clinical manifestations. Hence, designing effective therapies to either prevent or treat CHIKV infection is of paramount importance. Interestingly, monoclonal antibodies (mAbs) are known to be significantly important in mediating protective immunity in CHIV infection. During the last decades, numerous animal studies have reported the protective and prophylactic efficacy of human and mouse anti-CHIKV mAbs isolated from convalescent patients. However, the therapeutic benefits of these anti-CHIKV mAbs can be limited by multiple factors. Thus, it becomes pertinent to better understand the CHIKV infection dynamics, mitigate the undesired mAbs-associated effects and improve therapies. In this review, we critically discuss CHIKV antiviral infectious mechanisms and address how the improved understanding of the latter may pave the way to better targeted immunotherapies.

scholarly journals A Review of Chikungunya Virus-induced Arthralgia: Clinical Manifestations, Therapeutics, and Pathogenesis

2016 ◽  
Vol 10 (1) ◽  
pp. 129-140 ◽  
Author(s):  
Brad A. Goupil ◽  
Christopher N. Mores
Keyword(s):  
Clinical Research ◽  
Chikungunya Virus ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Western Hemisphere ◽  
Joint Disease ◽  
Chikv Infection ◽  
Initial Infection ◽  
Current State

Background:Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that circulates predominantly in tropical and subtropical regions, potentially affecting over 1 billion people. Recently, an outbreak began in the western hemisphere and has resulted in over 1.8 million reported suspected cases. Infection often results in severe fever, rash and debilitating polyarthralgia lasting weeks to months. Additionally, the current literature reports that CHIKV can result in a severe chronic arthralgia and/or arthritis that can last months to years following the initial infection.Objective:The purpose of this review is to evaluate the literature and summarize the current state of knowledge regarding CHIKV-associated disease, including clinical presentation, diagnosis, risk factors for development of severe disease, treatment, and pathogenesis in human patients. Additionally, recommendations are presented regarding avenues for clinical research to help further elucidate the pathogenesis of joint disease associated with CHIKV infection.Conclusion:While there is an association between initial CHIKV infection and acute disease, a causal relationship with development of chronic arthralgia has not been established at this time. Potential causes of chronic CHIKV-induced arthritis have been postulated, including viral persistence, induction of autoimmune disease, and exacerbation of pre-existing joint disease. While there are numerous reports of chronic CHIKV-associated arthralgia and/or arthritis, there is currently no evidence of a definitive link between initial infection and development of chronic disease. Additional, prospective clinical research on CHIKV-associated disease is necessary to further determine the potential role of virus and development of chronic joint disease.

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