scholarly journals Signal Transducer and Activator of Transcription Factor 6 Signaling Contributes to Control Host Lung Pathology but Favors Susceptibility againstToxocara canisInfection

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Berenice Faz-López ◽  
Yadira Ledesma-Soto ◽  
Yolanda Romero-Sánchez ◽  
Elsa Calleja ◽  
Pablo Martínez-Labat ◽  
...  
Keyword(s):  
Toxocara Canis ◽  
Lung Pathology ◽  
Activated Macrophages ◽  
Wild Type ◽  
Gastrointestinal Helminths ◽  
Th2 Response ◽  
Alternatively Activated Macrophages ◽  
Severe Pathology ◽  
Alternatively Activated

UsingSTAT6−/−BALB/c mice, we have analyzed the role of STAT6-induced Th2 response in determining the outcome of experimental toxocariasis caused by embryonated eggs of the helminth parasiteToxocara canis. FollowingT. canisinfection wild-type BALB/c mice developed a strong Th2-like response, produced high levels of IgG1, IgE, and IL-4, recruited alternatively activated macrophages, and displayed a moderate pathology in the lungs; however, they harbored heavy parasite loads in different tissues. In contrast, similarly infectedSTAT6−/−BALB/c mice mounted a weak Th2-like response, did not recruit alternatively activated macrophages, displayed a severe pathology in the lungs, but efficiently controlledT. canisinfection. These findings demonstrate that Th2-like response induced via STAT6-mediated signaling pathway mediates susceptibility to larval stage ofT. canis. Furthermore, they also indicate that unlike most gastrointestinal helminths, immunity against larvae ofT. canisis not mediated by a Th2-dominant response.

scholarly journals Identification of Caspase-6 as a New Regulator of Alternatively Activated Macrophages

2016 ◽  
Vol 291 (33) ◽  
pp. 17450-17466 ◽  
Author(s):  
Yongfang Yao ◽  
Qian Shi ◽  
Bing Chen ◽  
Qingsong Wang ◽  
Xinda Li ◽  
...  
Keyword(s):  
Cell Invasion ◽  
Protein Composition ◽  
Alternative Activation ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Protein Levels ◽  
Caspase 6 ◽  
Alternatively Activated

Alternatively activated macrophages (AAMs) play essential roles in the promotion of tissue remodeling, vasculogenesis, and tumor progression; however, the detailed mechanisms underlying the activation of AAMs remain largely unknown. Here, by using quantitative proteomic analysis, we identified 62 proteins that were up-regulated in IL-4-induced macrophages. Among these, Caspase-6 was increased significantly. Caspase-6 is important in the apoptotic signaling pathway; however, its role in non-apoptosis is also reported. Here, we first examined the non-apoptotic role of Caspase-6 in the alternative activation of macrophages after administration of IL-4, 4T1 tumor conditional medium, or co-culture with 4T1 cells. Both treatments promoted alternative activation of RAW264.7 cells and primary macrophages, whereas disruption of caspase-6 expression and activity could markedly suppress the biomarker levels of AAMs. Overexpression of Caspase-6 could significantly promote the activation of AAMs. Importantly, we further present evidence that caspase-6 could regulate breast cancer cell invasion by modulating MMP-2 and MMP-9 expression in 4T1 tumor-associated macrophages, as ablation of protein levels or activity of caspase-6 suppressed tumor cell invasion in vitro. In conclusion, the observed results markedly expanded our views of the dynamic changes in protein composition during alternative activation of macrophages, and they revealed a critical new role of caspase-6 in regulating this cellular biological process, which suggested that caspase-6 might be a key nod molecule to regulate immunological steady-state and be a therapeutic candidate for tumor immunotherapy.

scholarly journals The Role of Hypoxia-Induced Mitogenic Factor in Organ-Specific Inflammation in the Lung and Liver: Key Concepts and Gaps in Knowledge Regarding Molecular Mechanisms of Acute or Immune-Mediated Liver Injury

2021 ◽  
Vol 22 (5) ◽  
pp. 2717
Author(s):  
Sananda Pai ◽  
Dolores B. Njoku
Keyword(s):  
Clinical Trials ◽  
Liver Injury ◽  
Acute Liver Injury ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Mitogenic Factor ◽  
Immune Mediated ◽  
Organ Specific ◽  
Alternatively Activated

Hypoxia-induced mitogenic factor (HIMF), which is also known as resistin-like molecule α (RELM-α), found in inflammatory zone 1 (FIZZ1), or resistin-like alpha (retlna), is a cysteine-rich secretory protein and cytokine. HIMF has been investigated in the lung as a mediator of pulmonary fibrosis, inflammation and as a marker for alternatively activated macrophages. Although these macrophages have been found to have a role in acute liver injury and acetaminophen toxicity, few studies have investigated the role of HIMF in acute or immune-mediated liver injury. The aim of this focused review is to analyze the literature and examine the effects of HIMF and its human homolog in organ-specific inflammation in the lung and liver. We followed the guidelines set by PRISMA in constructing this review. The relevant checklist items from PRISMA were included. Items related to meta-analysis were excluded because there were no randomized controlled clinical trials. We found that HIMF was increased in most models of acute liver injury and reduced damage from acetaminophen-induced liver injury. We also found strong evidence for HIMF as a marker for alternatively activated macrophages. Our overall risk of bias assessment of all studies included revealed that 80% of manuscripts demonstrated some concerns in the randomization process. We also demonstrated some concerns (54.1%) and high risk (45.9%) of bias in the selection of the reported results. The need for randomization and reduction of bias in the reported results was similarly detected in the studies that focused on HIMF and the liver. In conclusion, we propose that HIMF could be utilized as a marker for M2 macrophages in immune-mediated liver injury. However, we also detected the need for randomized clinical trials and additional experimental and human prospective studies in order to fully comprehend the role of HIMF in acute or immune-mediated liver injury.

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