-
PloS One 2024Tear matrix metalloproteinase (MMP)-9 is an inflammatory signal in patients with dry eye (DE). In the present study, to understand the action mechanism of probiotic...
Tear matrix metalloproteinase (MMP)-9 is an inflammatory signal in patients with dry eye (DE). In the present study, to understand the action mechanism of probiotic LB101 (Lactobacillus plantarum NK151 and Bifidobacterium bifidum NK175 [4:1] mix) against DE, we investigated its effect on tear amount and inflammatory marker expression levels in mice with unilateral exorbital lacrimal gland excision/atropine-benzalkonium chloride application (EB) or fecal microbiota transplantation from mice with EB (eFMT). Oral gavage of LB101 increased EB-suppressed tear amount and decreased EB-induced blinking number. Furthermore, LB101 decreased EB-induced TNF-α, IL-1β, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva, while EB-suppressed IL-10 and occludin expression increased. LB101 also decreased EB-induced TNF-α and IL-1β expression and NF-κB+CD11c+ cell population in the colon. eFMT also decreased tear amount and increased blinking number in the transplanted mice. eFMT increased TNF-α, IL-1β, and MMP-9 expression and TNF-α+ and NF-κB+CD11c+ cell populations in the conjunctiva and TNF-α and IL-1β expression and NF-κB+CD11c+ cell populations in the colon. Oral gavage of LB101 increased eFMT-suppressed tear amount and decreased eFMT-induced blinking number. Furthermore, LB101 decreased TNF-α, IL-1β, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva and TNF-α and IL-1β expression and NF-κB+CD11c+ cell population in the colon, while eFMT-suppressed IL-10 and occludin expression decreased. Furthermore, LB101 increased eFMT-suppressed Muribaculaceae, Prevotellaceae, and Lactobacillaceae populations in the gut microbiota, while eFMT-induced Bacteroidaceae population decreased. These findings suggest that DE may cause gut dysbiosis, which may be a risk factor for DE, and LB101 may alleviate DE with gut inflammation by suppressing the expression of MMP-9 and proinflammatory cytokines TNF-α and IL-1β with the regulation of gut microbiota-involved NF-κB signaling.
Topics: Animals; Matrix Metalloproteinase 9; Dry Eye Syndromes; Gastrointestinal Microbiome; Mice; NF-kappa B; Probiotics; Signal Transduction; Mice, Inbred C57BL; Tears; Fecal Microbiota Transplantation; Tumor Necrosis Factor-alpha; Conjunctiva
PubMed: 38885258
DOI: 10.1371/journal.pone.0303423 -
Frontiers in Immunology 2024Sepsis is a life-threatening inflammatory condition caused by dysregulated host responses to infection. Extracellular cold-inducible RNA-binding protein (eCIRP) is a...
INTRODUCTION
Sepsis is a life-threatening inflammatory condition caused by dysregulated host responses to infection. Extracellular cold-inducible RNA-binding protein (eCIRP) is a recently discovered damage-associated molecular pattern that causes inflammation and organ injury in sepsis. Kupffer cells can be activated and polarized to the inflammatory M1 phenotype, contributing to tissue damage by producing proinflammatory mediators. We hypothesized that eCIRP promotes Kupffer cell M1 polarization in sepsis.
METHODS
We stimulated Kupffer cells isolated from wild-type (WT) and TLR4 mice with recombinant mouse (rm) CIRP (i.e., eCIRP) and assessed supernatant IL-6 and TNFα levels by ELISA. The mRNA expression of iNOS and CD206 for M1 and M2 markers, respectively, was assessed by qPCR. We induced sepsis in WT and CIRP mice by cecal ligation and puncture (CLP) and assessed iNOS and CD206 expression in Kupffer cells by flow cytometry.
RESULTS
eCIRP dose- and time-dependently increased IL-6 and TNFα release from WT Kupffer cells. In TLR4 Kupffer cells, their increase after eCIRP stimulation was prevented. eCIRP significantly increased iNOS gene expression, while it did not alter CD206 expression in WT Kupffer cells. In TLR4 Kupffer cells, however, iNOS expression was significantly decreased compared with WT Kupffer cells after eCIRP stimulation. iNOS expression in Kupffer cells was significantly increased at 20 h after CLP in WT mice. In contrast, Kupffer cell iNOS expression in CIRP mice was significantly decreased compared with WT mice after CLP. CD206 expression in Kupffer cells was not different across all groups. Kupffer cell M1/M2 ratio was significantly increased in WT septic mice, while it was significantly decreased in CIRP mice compared to WT mice after CLP.
CONCLUSION
Our data have clearly shown that eCIRP induces Kupffer cell M1 polarization via TLR4 pathway in sepsis, resulting in overproduction of inflammatory cytokines. eCIRP could be a promising therapeutic target to attenuate inflammation by preventing Kupffer cell M1 polarization in sepsis.
Topics: Animals; Kupffer Cells; Sepsis; Mice; Mice, Knockout; RNA-Binding Proteins; Mice, Inbred C57BL; Toll-Like Receptor 4; Male; Nitric Oxide Synthase Type II; Disease Models, Animal; Inflammation; Tumor Necrosis Factor-alpha; Mannose Receptor; Interleukin-6
PubMed: 38881891
DOI: 10.3389/fimmu.2024.1411930 -
Medicine Jun 2024To investigate the efficacy of 3 root canal sealants such as AH Plus, GuttaFlow and iRoot SP combined with warm gutta-percha vertical compression technique in the...
To investigate the efficacy of 3 root canal sealants such as AH Plus, GuttaFlow and iRoot SP combined with warm gutta-percha vertical compression technique in the treatment of dental pulp disease. This was a single-center retrospective study. 180 patients with dental pulp disease were divided into AH Plus group (n = 60), GuttaFlow group (n = 60) and iRoot SP group (n = 60) according to the different treatment methods. Patients in different groups were treated with corresponding root canal sealant combined with warm gutta-percha vertical compression technique. The quality of root canal filling, filling time, filling area ratio, the incidence of pain after operation, serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and efficacy at 6 months after operation were compared among the 3 groups, respectively. The filling time in the GuttaFlow group and the iRoot SP group was significantly shorter than that in the AH Plus group (P < .001). There were significant differences in pain grade (P = .015) and pain rate (P = .016) among the 3 groups, and the pain rate in the GuttaFlow group and the iRoot SP group was significantly lower than that in the AH Plus group (P = .016). The time-point effect, intergroup effect and time-groups effect of serum TNF-α and IL-6 were significantly different (P < .001), and the levels of the 3 groups after treatment were significantly lower than those before treatment (P < .05), and the levels were significantly lower in the GuttaFlow group and the iRoot SP group (P < .05). There were significant differences in efficacy grading and effective rate among the 3 groups (P = .028), and the effective rate of iRoot SP group was significantly higher than that of AH Plus group (P < .05). The iRoot SP or GuttaFlow as root canal sealant combined with warm gutta-percha vertical compression technique in the treatment of dental pulp disease is better than AH Plus, and the former one can shorten the filling time, relieve the postoperative pain and improve the inflammatory response, but the long-term apical sealing effect of iRoot SP is better than GuttaFlow.
Topics: Humans; Female; Male; Retrospective Studies; Adult; Root Canal Filling Materials; Gutta-Percha; Dental Pulp Diseases; Interleukin-6; Middle Aged; Tumor Necrosis Factor-alpha; Treatment Outcome; Young Adult; Drug Combinations; Dimethylpolysiloxanes
PubMed: 38875398
DOI: 10.1097/MD.0000000000038414 -
Science Advances Jun 2024Fibrosis-associated fibroblasts have been identified across various fibrotic disorders, but not in the context of biomaterials, fibrotic encapsulation, and the foreign...
Fibrosis-associated fibroblasts have been identified across various fibrotic disorders, but not in the context of biomaterials, fibrotic encapsulation, and the foreign body response. In other fibrotic disorders, a fibroblast subpopulation defined by Thy-1 loss is strongly correlated with fibrosis yet we do not know what promotes Thy-1 loss. We have previously shown that Thy-1 is an integrin regulator enabling normal fibroblast mechanosensing, and here, leveraging nonfibrotic microporous annealed particle (MAP) hydrogels versus classical fibrotic bulk hydrogels, we demonstrate that mice mount a fibrotic response to MAP gels that includes inflammatory signaling. We found that a distinct and cryptic α-smooth muscle actin-positive Thy-1 fibroblast population emerges in response to interleuklin-1β (IL-1β) and tumor necrosis factor-α (TNFα). Furthermore, IL-1β/TNFα-induced Thy-1 fibroblasts consist of two distinct subpopulations that are strongly proinflammatory. These findings illustrate the emergence of a unique proinflammatory, profibrotic fibroblast subpopulation that is central to fibrotic encapsulation of biomaterials.
Topics: Animals; Fibrosis; Thy-1 Antigens; Biocompatible Materials; Mice; Fibroblasts; Hydrogels; Tumor Necrosis Factor-alpha; Interleukin-1beta; Mice, Knockout
PubMed: 38875340
DOI: 10.1126/sciadv.adf2675 -
International Journal of Implant... Jun 2024This study aimed to evaluate the potential of Endothelin-1 (ET-1), a peptide derived from vascular endothelial cells, as a biomarker for diagnosing peri-implant diseases.
PURPOSE
This study aimed to evaluate the potential of Endothelin-1 (ET-1), a peptide derived from vascular endothelial cells, as a biomarker for diagnosing peri-implant diseases.
METHODS
A cohort of 29 patients with a total of 76 implants was included in this study and subsequently divided into three groups based on peri-implant clinical parameters and radiographic examination: healthy (peri-implant health) (n = 29), mucositis (n = 22), and peri-implantitis (n = 25) groups. The levels of ET-1 (ρg/site) and interleukin (IL)-1β (ρg/site) in peri-implant sulcus fluid (PISF) samples were determined using enzyme immunoassay. Statistical analyses were conducted using Kruskal-Wallis and Steel-Dwass tests. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic performance of the biomarkers.
RESULTS
ET-1 levels were significantly elevated in the peri-implantitis group compared to those in the healthy group, and were highest in the peri-implant mucositis group. Additionally, IL-1β levels were significantly higher in the peri-implantitis group than those in the healthy group. ROC curve analysis indicated that ET-1 exhibited superior area under the curve values, sensitivity, and specificity compared to those of IL-1β.
CONCLUSIONS
Our findings suggest that the presence of ET-1 in PISF plays a role in peri-implant diseases. Its significantly increased expression in peri-implant mucositis indicates its potential for enabling earlier and more accurate assessments of peri-implant inflammation when combined with conventional examination methods.
Topics: Humans; Endothelin-1; Peri-Implantitis; Cross-Sectional Studies; Male; Female; Biomarkers; Middle Aged; Interleukin-1beta; Dental Implants; Adult; Mucositis; Gingival Crevicular Fluid; Aged; ROC Curve
PubMed: 38874661
DOI: 10.1186/s40729-024-00551-0 -
Journal of Infection in Developing... May 2024Studies in different populations have shown that single-nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha (TNFα) and TNF receptors 1 and 2 (TNFR1 and...
INTRODUCTION
Studies in different populations have shown that single-nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha (TNFα) and TNF receptors 1 and 2 (TNFR1 and TNFR2) may be involved in the pathogenesis of lepromatous leprosy (LL). To further explore the results in a Mexican population, we compared the frequencies of the polymorphisms in - 308 G>A TNFA (rs1800629), - 383 A>C TNFRS1A (rs2234649), and + 196 T >G TNFSR1B (rs1061622) genes in LL patients (n = 133) and healthy subjects (n = 198).
METHODOLOGY
The genotyping was performed with the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) technique. Statistical analysis was performed using the χ2 test, within the 95% confidence interval. Odds ratios (OR) were calculated and Hardy-Weinberg equilibrium was verified for all control subjects and patients.
RESULTS
We found an association between the TNFSR1 -383 A>C genotype and the risk of lepromatous leprosy when leprosy patients were compared to controls (OR = 1.71, CI: 1.08-2.69, p = 0.02). Furthermore, it was also associated with the risk of LL in a dominant model (AC + CC vs AA, OR: 1.65, 95% CI: 1.05-2.057, p = 0.02). Similar genotype and allele frequencies for the SNPs TNFA - 308 G>A and TNFSR2 + 196 T>G were observed between leprosy patients and healthy subjects.
CONCLUSIONS
The TNFSR1 -383 A>C could be a potential marker for the identification of high-risk populations. However, additional studies, using larger samples of different ethnic populations, are required.
Topics: Humans; Mexico; Male; Female; Adult; Polymorphism, Single Nucleotide; Middle Aged; Leprosy, Lepromatous; Genetic Predisposition to Disease; Receptors, Tumor Necrosis Factor, Type I; Tumor Necrosis Factor-alpha; Receptors, Tumor Necrosis Factor, Type II; Young Adult; Aged; Gene Frequency; Polymorphism, Restriction Fragment Length; Case-Control Studies; Genotype; Adolescent; Polymerase Chain Reaction
PubMed: 38865403
DOI: 10.3855/jidc.17658 -
Biology Direct Jun 2024Glioma is a common tumor that occurs in the brain and spinal cord. Hypoxia is a crucial feature of the tumor microenvironment. Tumor-associated macrophages/microglia...
BACKGROUND
Glioma is a common tumor that occurs in the brain and spinal cord. Hypoxia is a crucial feature of the tumor microenvironment. Tumor-associated macrophages/microglia play a crucial role in the advancement of glioma. This study aims to illuminate the detailed mechanisms by which hypoxia regulates microglia and, consequently, influences the progression of glioma.
METHODS
The glioma cell viability and proliferation were analyzed by cell counting kit-8 assay and 5-ethynyl-2'-deoxyuridine assay. Wound healing assay and transwell assay were implemented to detect glioma cell migration and invasion, respectively. Enzyme-linked immunosorbent assay was conducted to detect protein levels in cell culture medium. The protein levels in glioma cells and tumor tissues were evaluated using western blot analysis. The histological morphology of tumor tissue was determined by hematoxylin-eosin staining. The protein expression in tumor tissues was determined using immunohistochemistry. Human glioma xenograft in nude mice was employed to test the influence of hypoxic microglia-derived interleukin-1beta (IL-1β) and heparanase (HPSE) on glioma growth in vivo.
RESULTS
Hypoxic HMC3 cells promoted proliferation, migration, and invasion abilities of U251 and U87 cells by secreting IL-1β, which was upregulated by hypoxia-induced activation of hypoxia inducible factor-1alpha (HIF-1α). Besides, IL-1β from HMC3 cells promoted glioma progression and caused activation of nuclear factor-κB (NF-κB) and upregulation of HPSE in vivo. We also confirmed that IL-1β facilitated HPSE expression in U251 and U87 cells by activating NF-κB. Hypoxic HMC3 cells-secreted IL-1β facilitated the proliferation, migration, and invasion of U251 and U87 cells via NF-κB-mediated upregulation of HPSE expression. Finally, we revealed that silencing HPSE curbed the proliferation and metastasis of glioma in mice.
CONCLUSION
Hypoxia-induced activation of HIF-1α/IL-1β axis in microglia promoted glioma progression via NF-κB-mediated upregulation of HPSE expression.
Topics: Glioma; Interleukin-1beta; Microglia; Animals; NF-kappa B; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Mice; Glucuronidase; Up-Regulation; Cell Line, Tumor; Mice, Nude; Disease Progression; Brain Neoplasms; Cell Proliferation; Cell Movement; Hypoxia
PubMed: 38863009
DOI: 10.1186/s13062-024-00487-w -
Molecular Medicine (Cambridge, Mass.) Jun 2024Studies have highlighted a possible crosstalk between the pathogeneses of COVID-19 and systemic lupus erythematosus (SLE); however, the interactive mechanisms remain...
BACKGROUND
Studies have highlighted a possible crosstalk between the pathogeneses of COVID-19 and systemic lupus erythematosus (SLE); however, the interactive mechanisms remain unclear. We aimed to elucidate the impact of COVID-19 on SLE using clinical information and the underlying mechanisms of both diseases.
METHODS
RNA-seq datasets were used to identify shared hub gene signatures between COVID-19 and SLE, while genome-wide association study datasets were used to delineate the interaction mechanisms of the key signaling pathways. Finally, single-cell RNA-seq datasets were used to determine the primary target cells expressing the shared hub genes and key signaling pathways.
RESULTS
COVID-19 may affect patients with SLE through hematologic involvement and exacerbated inflammatory responses. We identified 14 shared hub genes between COVID-19 and SLE that were significantly associated with interferon (IFN)-I/II. We also screened and obtained four core transcription factors related to these hub genes, confirming the regulatory role of the IFN-I/II-mediated Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway on these hub genes. Further, SLE and COVID-19 can interact via IFN-I/II and IFN-I/II receptors, promoting the levels of monokines, including interleukin (IL)-6/10, tumor necrosis factor-α, and IFN-γ, and elevating the incidence rate and risk of cytokine release syndrome. Therefore, in SLE and COVID-19, both hub genes and core TFs are enriched within monocytes/macrophages.
CONCLUSIONS
The interaction between SLE and COVID-19 promotes the activation of the IFN-I/II-triggered JAK-STAT signaling pathway in monocytes/macrophages. These findings provide a new direction and rationale for diagnosing and treating patients with SLE-COVID-19 comorbidity.
Topics: Humans; COVID-19; Lupus Erythematosus, Systemic; Signal Transduction; SARS-CoV-2; Genome-Wide Association Study; Female; Janus Kinases; STAT Transcription Factors; Male; Transcriptome; Gene Expression Profiling; Multiomics
PubMed: 38862942
DOI: 10.1186/s10020-024-00851-6 -
Cell Death & Disease Jun 2024Methicillin-resistant Staphylococcus aureus (MRSA) is the most common causative agent of acute bacterial skin and skin-structure infections (ABSSSI), one of the major...
Methicillin-resistant Staphylococcus aureus (MRSA) is the most common causative agent of acute bacterial skin and skin-structure infections (ABSSSI), one of the major challenges to the health system worldwide. Although the use of antibiotics as the first line of intervention for MRSA-infected wounds is recommended, important side effects could occur, including cytotoxicity or immune dysregulation, thus affecting the repair process. Here, we show that the oxazolidinone antibiotic linezolid (LZD) impairs wound healing by aberrantly increasing interleukin 1 β (IL-1β) production in keratinocytes. Mechanistically, LZD triggers a reactive oxygen species (ROS)-independent mitochondrial damage that culminates in increased tethering between the endoplasmic reticulum (ER) and mitochondria, which in turn activates the NLR family pyrin domain-containing 3 (NLRP3) inflammasome complex by promoting its assembly to the mitochondrial surface. Downregulation of ER-mitochondria contact formation is sufficient to inhibit the LZD-driven NLRP3 inflammasome activation and IL-1β production, restoring wound closure. These results identify the ER-mitochondria association as a key factor for NLRP3 activation and reveal a new mechanism in the regulation of the wound healing process that might be clinically relevant.
Topics: NLR Family, Pyrin Domain-Containing 3 Protein; Mitochondria; Wound Healing; Endoplasmic Reticulum; Humans; Animals; Inflammasomes; Interleukin-1beta; Reactive Oxygen Species; Mice; Keratinocytes; Mice, Inbred C57BL
PubMed: 38862500
DOI: 10.1038/s41419-024-06765-9 -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... May 2024To investigate the mechanisms that mediate the neuroprotective effect of the intestinal microbial metabolite sodium butyrate (NaB) in a mouse model of Parkinson's...
OBJECTIVE
To investigate the mechanisms that mediate the neuroprotective effect of the intestinal microbial metabolite sodium butyrate (NaB) in a mouse model of Parkinson's disease (PD) the gut-brain axis.
METHODS
Thirty-nine 7-week-old male C57BL/6J mice were randomized equally into control group, PD model group, and NaB treatment group. In the latter two groups, PD models were established by intraperitoneal injection of 30 mg/kg 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) once daily for 5 consecutive days, and normal saline was injected in the control group. After modeling, the mice received daily gavage of NaB (300 mg/kg) or an equal volume of saline for 14 days. Behavioral tests were carried out to assess the changes in motor function of the mice, and Western blotting was performed to detect the expressions of tyrosine hydroxylase (TH) and -synuclein (-syn) in the striatum and nuclear factor-κB (NF-κB), tumor necrosis factor (TNF-), interleukin 6 (IL-6), and the tight junction proteins ZO-1, Occludin, and Claudinin the colon. HE staining was used to observe inflammatory cell infiltration in the colon of the mice. RNA sequencing analysis was performed to identify the differentially expressed genes in mouse colon tissues, and their expressions were verified using qRT-PCR and Western blotting.
RESULTS
The mouse models of PD with NaB treatment showed significantly increased movement speed and pulling strength of the limbs with obviously upregulated expressions of TH, Occludin, and Claudin and downregulated expressions of -syn, NF-κB, TNF-, and IL-6 (all < 0.05). HE staining showed that NaB treatment significantly ameliorated inflammatory cell infiltration in the colon of the PD mice. RNA sequencing suggested that Bmal1 gene probably mediated the neuroprotective effect of NaB in PD mice ( < 0.05).
CONCLUSION
NaB can improve motor dysfunction, reduce dopaminergic neuron loss in the striatum, and ameliorate colonic inflammation in PD mice possibly through a mechanism involving Bmal1.
Topics: Animals; Mice; Butyric Acid; Male; Mice, Inbred C57BL; Neuroprotective Agents; Disease Models, Animal; Parkinson Disease; alpha-Synuclein; Tumor Necrosis Factor-alpha; NF-kappa B; Interleukin-6; Tyrosine 3-Monooxygenase; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Corpus Striatum; Occludin; Brain-Gut Axis
PubMed: 38862445
DOI: 10.12122/j.issn.1673-4254.2024.05.09