rHu MIP-1-alpha
- Known as:
- rHu MIP-1-a
- Catalog number:
- AK8250-0005
- Product Quantity:
- 5
- Category:
- -
- Supplier:
- Akro
- Gene target:
- rHu MIP-1-alpha
Related products to: rHu MIP-1-alpha
Related articles to: rHu MIP-1-alpha
- Persistent inflammation, immunosuppression, and catabolism syndrome (PIICS) is a major cause of prolonged morbidity and poor outcomes among critical illness survivors. We established long-term murine PIICS models using two peritonitis-induced sepsis methods-cecal ligation and puncture (CLP) and fecal suspension intraperitoneal injection (FSI)-and investigated their immunological and histopathological features over 2 months. Survivors were defined as PIICS model mice, with unoperated mice serving as controls. Following an intraperitoneal lipopolysaccharide (LPS; 10 mg/kg) challenge, 27 plasma cytokines and chemokines were quantified before and 20 h after administration, and survival was monitored for 14 days. Survivors of CLP and FSI exhibited sustained baseline elevations in inflammatory mediators (G-CSF, IL-7, CCL3/4) and reductions in anti-inflammatory cytokines (IL-13, TGF-β2) compared with those in controls. Following the LPS challenge, control mice showed robust cytokine induction, and 4 of 13 died, whereas both PIICS groups exhibited globally suppressed cytokine responses with no mortality (p = 0.011 vs. controls). Histopathological staining showed mild splenic macrophage infiltration at baseline in both PIICS groups. Upon LPS administration, pulmonary congestion, splenic macrophage infiltration, and neutrophil infiltration into the portal vein were observed. Intra-abdominal abscesses or granuloma-like masses occurred in 50% of CLP-PIICS mice. Collectively, these long-term PIICS models recapitulate key clinical features, including persistent dysregulated inflammation, impaired responsiveness to secondary stimuli, and chronic tissue pathology, providing a platform to investigate the transition from acute sepsis to PIICS and for preclinical testing of immune-restorative or metabolic interventions in survivors of sepsis. - Source: PubMed
Publication date: 2026/08/20
Tsuchida TakumiWada TakeshiMizugaki AsumiOda YoshitakaKayano KatsuhideYamakawa KazumaTanaka Shinya - PIWILs are RNA-binding proteins whose role in ischemic stroke remains poorly defined. Here, we investigated the contribution of PIWILs to post-ischemic neuroinflammation by using a mouse model of 1 h transient middle cerebral artery occlusion (tMCAo), followed by 6 or 24 h of reperfusion. Brain tissues, blood, and peripheral organs were collected to assess PIWIL expression, inflammatory responses, and brain damage. PIWIL1 and PIWIL2 were significantly upregulated in the cortex and striatum at 24 h post-ischemia, with PIWIL2 also increased in blood and peripheral tissues. Immunofluorescence analyses revealed cell-type-specific localization of PIWILs in neurons, astrocytes, and endothelial cells. Notably, siRNA-mediated silencing of PIWIL2 significantly reduced infarct volume. PIWIL2 silencing also attenuated NF-κB-p65 and phospho-IκBα levels in the peri-infarct cortex but not in the striatum, indicating region-specific modulation of NF-κB signaling and differentially reprogrammed systemic chemokine profiles, with selective upregulation of CCL3, CCL5, and CXCL13 and downregulation of CCL2, CCL17, CCL20, and CXCL1. Mechanistically, PIWIL2 interacted with IKKα and promoted activation of the NF-κB pathway, leading to RelA- and RelB-dependent transcriptional regulation of pro-inflammatory chemokines. Together, these findings identify PIWIL2 as an upstream regulator of NF-κB-dependent neuroinflammation that exacerbates ischemic brain injury and suggest PIWIL2 as a promising therapeutic target targeting post-stroke inflammatory damage. - Source: PubMed
Publication date: 2026/07/24
Patil Rohan MaheshLaudati GiusyGuida NatasciaRuggiero SilviaDi Muraglia NoemiAnzilotti SerenellaLanthaler JulianCoppola LuigiFormisano LuigiAnnunziato LucioEsposito ElgaPignataro Giuseppe - Radiotherapy elicits dual immunomodulatory effects in cancer, activating antitumor immunity while paradoxically inducing immunosuppression, which limits therapeutic efficacy. The molecular pathways mediating postradiation immune escape in hepatocellular carcinoma (HCC) remain poorly defined. Here, we elucidate a previously uncharacterized mechanism whereby radiotherapy drives the accumulation of CD200 tumor-associated macrophages (TAMs) that suppress eosinophil-mediated antitumor immunity in patients with HCC. Through single-cell RNA sequencing of postradiotherapy HCC specimens, we demonstrated that radiation-induced DNA damage activated the cytosolic DNA-sensing STING pathway in TAMs, triggering NF-κB-dependent CD200 upregulation independent of canonical type I interferon signaling. These radiation-induced CD200 TAMs exhibited an immunosuppressive phenotype and correlated with adverse clinical outcomes in HCC patients. Mechanistically, CD200 TAMs established an immunosuppressive axis by recruiting CCR1 eosinophils through CCL3-mediated chemotaxis, subsequently inhibiting their antitumor functions via CD200-CD200R engagement. This interaction comprehensively suppressed NF-κB activation in eosinophils, impaired their antigen-presenting capacity and Th2 cytokine secretion and abrogated their ability to support CD8 T-cell-mediated cytotoxicity. Therapeutic blockade of CD200R following radiotherapy restored eosinophil effector functions, promoted central memory T-cell formation, and significantly enhanced tumor control across multiple preclinical HCC models. Remarkably, CD200R antagonism sensitized PD-1-refractory "cold" tumors to radioimmunotherapy combinations, overcoming primary resistance. Our findings establish STING-driven CD200 TAM accumulation and subsequent eosinophil dysfunction as critical determinants of radioresistance, positioning CD200R blockade as a promising therapeutic strategy to potentiate radioimmunotherapy responses in patients with HCC. Graphical abstract of the study findings. Radiotherapy-induced STING signaling activation promotes the accumulation of CD200 TAMs. These CD200 TAMs facilitate the recruitment of eosinophils via the CCL3-CCR1 chemotaxis axis while simultaneously suppressing eosinophil-mediated antitumor activity through CD200-CD200R engagement (left panel). Targeted blockade of CD200R following radiotherapy unleashed the antitumor potential of eosinophils, leading to enhanced infiltration and effector function of CTLs (right panel). - Source: PubMed
Publication date: 2026/08/13
Li KunLi SiqiQiu DongboQiu XiushengYu HaoyuanXiong YiLiang WeiLiang ZhixingCheng ShuqunLi HuaQin YunfeiYang YangYe Linsen - Traumatic brain injury (TBI) involves both primary and secondary pathological processes, including hemorrhage, ischemia, edema, and neuroinflammation. Although tissue-derived exosomes have emerged as important mediators of intercellular communication within local tissue microenvironments, their role in TBI-associated inflammatory responses remains incompletely understood. This study integrated brain tissue-derived exosomal proteomics with publicly available hippocampal transcriptomic data to investigate the potential association between tissue-derived exosomes and chemotaxis-related inflammatory responses after TBI. Brain tissue-derived exosomes were isolated, characterized, and subjected to label-free proteomic analysis. Public hippocampal transcriptomic data from GSE173975 were analyzed, and differentially expressed proteins (DEPs) and genes (DEGs) were identified from the exosomal proteomic and transcriptomic datasets, respectively. Functional enrichment, co-enrichment, and protein-protein interaction network analyses were performed, followed by quantitative real-time PCR, exosomal western blotting, and Transwell migration assays for validation and functional assessment. In total, 190 DEPs and 465 DEGs were identified. Co-enrichment analyses highlighted immune- and inflammation-related processes, particularly chemotaxis-related processes and chemokine signaling. LGALS3 and ITGB2 were increased at the exosomal protein level in brain tissue-derived exosomes from TBI rats and also showed increased hippocampal mRNA expression, whereas CCL2, CCL3, and CCR5 were upregulated at the hippocampal mRNA level. Functionally, TBI-derived exosomes enhanced BV2 microglial migration in vitro. Overall, these findings suggest that injury-associated brain tissue-derived exosomes may be associated with chemotaxis-related inflammatory and pro-migratory responses after TBI. - Source: PubMed
Publication date: 2026/08/10
Chen Wei-CanChen Xin-LiLin Cheng-YeHuang Yang-ZiHe He-FanZhou Yi-LinLiu Yi-Bin - Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease with variable outcomes following functional endoscopic sinus surgery (FESS). Predictive biomarkers for post-FESS CRSwNP recurrence remain poorly defined. - Source: PubMed
Publication date: 2026/08/07
Dharia TiffanyZawacki MabelMaurer RieBergmark Regan WLee Stella EMaxfield Alice ZRoditi Rachel ELee Pui YHsu EvanLeSon CourtneyKratchmarov RadomirBalestrieri BarbaraLaidlaw Tanya MBuchheit Kathleen M