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International Journal of Molecular... Feb 2020The excellent clinical efficacy of anti-interleukin 17A (IL-17A) biologics on psoriasis indicates a crucial pathogenic role of IL-17A in this autoinflammatory skin... (Review)
Review
The excellent clinical efficacy of anti-interleukin 17A (IL-17A) biologics on psoriasis indicates a crucial pathogenic role of IL-17A in this autoinflammatory skin disease. IL-17A accelerates the proliferation of epidermal keratinocytes. Keratinocytes produce a myriad of antimicrobial peptides and chemokines, such as CXCL1, CXCL2, CXCL8, and CCL20. Antimicrobial peptides enhance skin inflammation. IL-17A is capable of upregulating the production of these chemokines and antimicrobial peptides in keratinocytes. CXCL1, CXCL2, and CXCL8 recruit neutrophils and CCL20 chemoattracts IL-17A-producing CCR6 immune cells, which further contributes to forming an IL-17A-rich milieu. This feed-forward pathogenic process results in characteristic histopathological features, such as epidermal hyperproliferation, intraepidermal neutrophilic microabscess, and dermal CCR6 cell infiltration. In this review, we focus on IL-17A and keratinocyte interaction regarding psoriasis pathogenesis.
Topics: Cell Proliferation; Chemokine CCL20; Chemokine CXCL1; Chemokine CXCL2; Epidermis; Humans; Interleukin-17; Interleukin-8; Keratinocytes; Neutrophils; Psoriasis
PubMed: 32070069
DOI: 10.3390/ijms21041275 -
JBRA Assisted Reproduction Aug 2022Endometritis is defined as an infection or inflammation of the endometrium. Endometritis is of two types: acute and chronic. Acute endometritis is the symptomatic acute... (Review)
Review
Endometritis is defined as an infection or inflammation of the endometrium. Endometritis is of two types: acute and chronic. Acute endometritis is the symptomatic acute inflammation of the endometrium, which upon examination with a microscope shows micro-abscess and neutrophil invasion in the superficial endometrium. One of its most common manifestations is postpartum endometritis. Chronic endometritis is a silent disease usually diagnosed on the workup of secondary amenorrhoea and infertility. An important cause of chronic endometritis is tuberculosis, especially in developing nations. Chronic and acute endometritis have been associated with poor reproductive outcomes. Worse outcomes have been reported for individuals with chronic endometritis. This is a scoping review of endometritis and its impact on fertility.
Topics: Endometritis; Endometrium; Female; Fertility; Humans; Infertility; Inflammation
PubMed: 35621273
DOI: 10.5935/1518-0557.20220015 -
Journal of Oral and Maxillofacial... 2019
PubMed: 31942132
DOI: 10.4103/jomfp.JOMFP_73_19 -
International Journal of Molecular... Jun 2021ANCA-associated vasculitis (AAV) comprises granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis... (Review)
Review
ANCA-associated vasculitis (AAV) comprises granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). While systemic vasculitis is a hallmark of all AAV, GPA is characterized by extravascular granulomatous inflammation, preferentially affecting the respiratory tract. The mechanisms underlying the emergence of neutrophilic microabscesses; the appearance of multinucleated giant cells; and subsequent granuloma formation, finally leading to scarred or destroyed tissue in GPA, are still incompletely understood. This review summarizes findings describing the presence and function of molecules and cells contributing to granulomatous inflammation in the respiratory tract and to renal inflammation observed in GPA. In addition, factors affecting or promoting the development of granulomatous inflammation such as microbial infections, the nasal microbiome, and the release of damage-associated molecular patterns (DAMP) are discussed. Further, on the basis of numerous results, we argue that, in situ, various ways of exposure linked with a high number of infiltrating proteinase 3 (PR3)- and myeloperoxidase (MPO)-expressing leukocytes lower the threshold for the presentation of an altered PR3 and possibly also of MPO, provoking the local development of ANCA autoimmune responses, aided by the formation of ectopic lymphoid structures. Although extravascular granulomatous inflammation is unique to GPA, similar molecular and cellular patterns can be found in both the respiratory tract and kidney tissue of GPA and MPA patients; for example, the antimicrobial peptide LL37, CD163 macrophages, or regulatory T cells. Therefore, we postulate that granulomatous inflammation in GPA or PR3-AAV is intertwined with autoimmune and destructive mechanisms also seen at other sites.
Topics: Animals; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Autoimmune Diseases; Autoimmunity; Biomarkers; Cell Movement; Disease Management; Disease Susceptibility; Granulomatosis with Polyangiitis; Humans; Immunity, Innate; Immunohistochemistry; Organ Specificity
PubMed: 34204207
DOI: 10.3390/ijms22126474 -
Neurology India 2023Melioidosis is a bacterial infection caused by Burkholderia pseudomallei that is endemic in Southeast Asia, northern Australia, and Africa. Neurological involvement is... (Review)
Review
BACKGROUND
Melioidosis is a bacterial infection caused by Burkholderia pseudomallei that is endemic in Southeast Asia, northern Australia, and Africa. Neurological involvement is rare and reported in 3-5% of total cases.
OBJECTIVE
The purpose of this study was to report a series of cases of melioidosis with neurological involvement and a brief review of the literature.
MATERIALS AND METHODS
We collected the data from six melioidosis patients having neurological involvement. Clinical, biochemical, and imaging findings were analyzed.
RESULT
All patients in our study were adults (age range 27 to 73 years). The presenting symptoms were fever of varying duration (range 15 days to 2 months). Altered sensorium was noted in five patients. Four cases had brain abscess, one had meningitis, and one had a spinal epidural abscess. All cases of brain abscesses were T2 hyperintense with an irregular wall showing central diffusion restriction and irregular peripheral enhancement. The trigeminal nucleus was involved in one patient, but there was no enhancement of the trigeminal nerve. Extension along the white matter tract was noted in two patients. Magnetic resonance (MR) spectroscopy done in two patients showed increased lipid/lactate and choline peak in both of them.
CONCLUSION
Melioidosis can present as multiple micro-abscesses in the brain. Involvement of the trigeminal nucleus and extension along the corticospinal tract may raise the possibility of infection by B. pseudomallei. Meningitis and dural sinus thrombosis, although rare, can be presenting features.
Topics: Adult; Humans; Middle Aged; Aged; Melioidosis; Magnetic Resonance Imaging; Brain Abscess; Brain; Lactic Acid
PubMed: 36861583
DOI: 10.4103/0028-3886.370442 -
Intensive Care Medicine Experimental Jul 2019Sepsis is a highly lethal disorder. Organ dysfunction in sepsis is not defined as a clinicopathological entity but rather by changes in clinical, physiological, or... (Review)
Review
BACKGROUND
Sepsis is a highly lethal disorder. Organ dysfunction in sepsis is not defined as a clinicopathological entity but rather by changes in clinical, physiological, or biochemical parameters. Pathogenesis and specific treatment of organ dysfunction in sepsis are unknown. The study of the histopathological correlate of organ dysfunction in sepsis will help understand its pathogenesis.
METHODS
We searched in PubMed, EMBASE, and Scielo for original articles on kidney, brain, and liver dysfunction in human sepsis. A defined search strategy was designed, and pertinent articles that addressed the histopathological changes in sepsis were retrieved for review. Only studies considered relevant in the field were discussed.
RESULTS
Studies on acute kidney injury (AKI) in sepsis reveal that acute tubular necrosis is less prevalent than other changes, indicating that kidney hypoperfusion is not the predominant pathogenetic mechanism of sepsis-induced AKI. Other more predominant histopathological changes are apoptosis, interstitial inflammation, and, to a lesser extent, thrombosis. Brain pathological findings include white matter hemorrhage and hypercoagulability, microabscess formation, central pontine myelinolysis, multifocal necrotizing leukoencephalopathy, metabolic changes, ischemic changes, and apoptosis. Liver pathology in sepsis includes steatosis, cholangiolitis and intrahepatic cholestasis, periportal inflammation, and apoptosis. There is no information on physiological or biochemical biomarkers of the histopathological findings.
CONCLUSIONS
Histopathological studies may provide important information for a better understanding of the pathogenesis of organ dysfunction in sepsis and for the design of potentially effective therapies. There is a lack of clinically available biomarkers for the identification of organ dysfunction as defined by the histological analysis.
PubMed: 31346833
DOI: 10.1186/s40635-019-0236-3 -
Frontiers in Pediatrics 2022More than 400 single gene defects have been identified as inborn errors of immunity, including many arising from genes encoding proteins that affect NF-κB activity. We... (Review)
Review
More than 400 single gene defects have been identified as inborn errors of immunity, including many arising from genes encoding proteins that affect NF-κB activity. We summarise the skin phenotypes in this subset of disorders and provide an overview of pathogenic mechanisms. NF-κB acts cell-intrinsically in basal epithelial cells during differentiation of skin appendages, influences keratinocyte proliferation and survival, and both responses to and amplification of inflammation, particularly TNF. Skin phenotypes include ectodermal dysplasia, reduction and hyperproliferation of keratinocytes, and aberrant recruitment of inflammatory cells, which often occur in combination. Phenotypes conferred by these rare monogenic syndromes often resemble those observed with more common defects. This includes oral and perineal ulceration and pustular skin disease as occurs with Behcet's disease, hyperkeratosis with microabscess formation similar to psoriasis, and atopic dermatitis. Thus, these genotype-phenotype relations provide diagnostic clues for this subset of IEIs, and also provide insights into mechanisms of more common forms of skin disease.
PubMed: 36733767
DOI: 10.3389/fped.2022.1098426 -
Frontiers in Immunology 2022Munro's microabscess is a typical pathological feature in the early psoriatic lesion, mainly characterized by the accumulation of neutrophils in the epidermis. DNA...
INTRODUCTION
Munro's microabscess is a typical pathological feature in the early psoriatic lesion, mainly characterized by the accumulation of neutrophils in the epidermis. DNA methylation microenvironment of Munro's microabscess and the crosstalk with transcription and its effect on neutrophils have not yet been revealed.
METHODS
Performed genome-wide DNA methylation analysis and further differential methylation analysis of psoriatic skin lesions with and without Munro's microabscess from two batch samples consisting of 114 former samples in the discovery stage and 21 newly-collected samples in the validation stage. Utilized GO, MEME, and other tools to conduct downstream analysis on differentially methylated sites (DMSs). Correlation analysis of methylation level and transcriptome data was also conducted.
RESULTS
We observed 647 overlapping DMSs associated with Munro's microabscess. Subsequently, GO pathway analysis revealed that DNA methylation might affect the physical properties associated with skin cells through focal adhesion and cellsubstrate junction and was likely to recruit neutrophils in the epidermis. Via the MEME tool, used to investigate the possible binding transcription factors (TFs) of 20 motifs around the 647 DMSs, it was found that DNA methylation regulated the binding of AP1 family members and the recruitment of neutrophils in the epidermis through the TGF-beta pathway and the TH17 pathway. Meanwhile, combined with our earlier transcriptome data, we found DNA methylation would regulate the expressions of CFDP, SIRT6, SMG6, TRAPPC9, HSD17B7, and KIAA0415, indicating these genes would potentially promote the process of Munro's microabscess.
DISCUSSION
In conclusion, DNA methylation may affect the course of psoriasis by regulating the progression of Munro's microabscess in psoriatic skin lesions.
Topics: Humans; DNA Methylation; Epigenesis, Genetic; Psoriasis; Skin; Abscess; Sirtuins
PubMed: 36569916
DOI: 10.3389/fimmu.2022.1057839 -
Journal of Translational Medicine Apr 2023A causal link between microbiota composition (dysbiosis) and oncogenesis has been demonstrated for several types of cancer. Neutrophils play a role in both immune...
BACKGROUND
A causal link between microbiota composition (dysbiosis) and oncogenesis has been demonstrated for several types of cancer. Neutrophils play a role in both immune protection against bacterial threats and carcinogenesis. This study aimed to characterise intratumoral bacteria in vulvar squamous cell carcinoma (VSCC) and their putative effect on neutrophil recruitment and cancer progression.
METHODS
Clinical material was obtained from 89 patients with VSCC. Next-generation sequencing (NGS) of 16S rRNA and quantitative polymerase chain reaction (qPCR) were used to detect bacterial species in VSCC. To verify neutrophil activation, CD66b expression in tumour specimens was analysed by immunohistochemistry (IHC). Subsequently, IHC was applied to detect the main neutrophil serine proteases (NSPs), cathepsin G (CTSG), neutrophil elastase (ELANE), and proteinase 3 (PRTN3) in VSCC.
RESULTS
Fusobacterium nucleatum and Pseudomonas aeruginosa were identified as tumour-promoting bacteria, and their presence was found to be associated with a shorter time to progression in VSCC patients. Furthermore, high abundance of CD66b, the neutrophil activation marker, in VSCC samples, was found to relate to poor survival of patients with VSCC. The selected NSPs were shown to be expressed in vulvar tumours, also within microabscess. The increased numbers of microabscesess were correlated with poor survival in VSCC patients.
CONCLUSIONS
Our results show that neutrophilic inflammation seem to be permissive for tumour-promoting bacteria growth in VSCC. The findings provide new therapeutic opportunities, such as based on shifting the balance of neutrophil populations to those with antitumorigenic activity and on targeting NSPs produced by activated neutrophils at the inflammation sites.
Topics: Female; Humans; Vulvar Neoplasms; RNA, Ribosomal, 16S; Carcinoma, Squamous Cell; Inflammation; Epithelial Cells; Tumor Microenvironment
PubMed: 37118737
DOI: 10.1186/s12967-023-04113-7