scholarly journals Dysregulation of tryptophan catabolism at the host-skin microbiota interface in Hidradenitis Suppurativa

2020 ◽  
Author(s):  
Laure Guenin-Mace ◽  
Jean-David Morel ◽  
Jean-Marc Doisne ◽  
Angele Schiavo ◽  
Lysiane Boulet ◽  
...  
Keyword(s):  
Hidradenitis Suppurativa ◽  
Skin Lesions ◽  
Kynurenine Pathway ◽  
Dermal Fibroblasts ◽  
Unknown Etiology ◽  
Skin Microbiota ◽  
Aryl Hydrocarbon ◽  
Metabolomic Profiling ◽  
Tryptophan Catabolism ◽  
Chronic Skin

Hidradenitis Suppurativa (HS) is a chronic skin disorder of unknown etiology that manifests as recurrent, painful lesions. Cutaneous dysbiosis and unresolved inflammation are hallmarks of active HS, but their origin and interplay remain unclear. Our metabolomic profiling of HS skin revealed an abnormal induction of the kynurenine pathway (KP) of tryptophan catabolism in dermal fibroblasts correlating with the release of KP-inducing cytokines by inflammatory cell infiltrates. Notably, over-activation of the KP in lesional skin was associated with local and systemic depletion in tryptophan. Yet the skin microbiota normally degrades host tryptophan into indoles regulating tissue inflammation via engagement of the Aryl Hydrocarbon Receptor (AHR). In HS skin lesions, we detected contextual defects in AHR activation coinciding with impaired production of bacteria-derived AHR agonists and decreased incidence of AHR ligand-producing bacteria in the resident flora. Dysregulation of tryptophan catabolism at the skin-microbiota interface thus provides a mechanism linking the immunological and microbiological features of HS lesions. In addition to revealing metabolic alterations in HS patients, our study suggests that correcting AHR signaling would help restore immune homeostasis in HS skin.

scholarly journals Tryptophan Catabolism in Chronic Viral Infections: Handling Uninvited Guests

2015 ◽  
Vol 8 ◽  
pp. IJTR.S26862 ◽  
Author(s):  
Vikram Mehraj ◽  
Jean-Pierre Routy
Keyword(s):  
Viral Infections ◽  
Acute Infection ◽  
Kynurenine Pathway ◽  
Therapeutic Interventions ◽  
Indoleamine 2 ◽  
Aryl Hydrocarbon ◽  
Chronic Viral Infections ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Tryptophan Catabolism

L-Tryptophan (L-Trp) is an essential amino acid that possesses diverse metabolic, neurological, and immunological roles spanning from the synthesis of proteins, neurotransmitter serotonin, and neurohormone melatonin, to its degradation into immunosuppressive catabolites by indoleamine-2, 3-dioxygenase (IDO) in the kynurenine pathway (KP). Trp catabolites, by activating aryl hydrocarbon receptor (AhR), play an important role in antimicrobial defense and immune regulation. IDO/AhR acts as a double-edged sword by both depleting L-Trp to starve the invaders and by contributing to the state of immunosuppression with microorganisms that were not cleared during acute infection. Pathogens experiencing Trp deprivation by IDO-mediated degradation include certain bacteria, parasites, and less likely viruses. However, chronic viral infections highjack the host immune response to create a state of disease tolerance via kynurenine catabolites. This review covers the latest data involving chronic viral infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes, and cytomegalovirus (CMV) and their cellular interplay with Trp catabolites. Strategies developed by viruses to escape immune control also represent new avenues for therapeutic interventions based on Trp metabolism.

scholarly journals Plant Antimicrobial Peptides as Potential Tool for Topic Treatment of Hidradenitis Suppurativa

2021 ◽  
Vol 12 ◽  
Author(s):  
Carlos André dos Santos-Silva ◽  
Paola Maura Tricarico ◽  
Lívia Maria Batista Vilela ◽  
Ricardo Salas Roldan-Filho ◽  
Vinícius Costa Amador ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Hidradenitis Suppurativa ◽  
Skin Lesions ◽  
Biological Drugs ◽  
Medical Treatments ◽  
Anti Inflammatory ◽  
Chronic Skin ◽  
Therapeutic Compounds ◽  
Inflammatory Molecules ◽  
Variable Condition

Among chronic skin autoinflammatory diseases, Hidradenitis Suppurativa (HS) stands out for its chronicity, highly variable condition, and profound impact on the patients’ quality of life. HS is characterized by suppurative skin lesions in diverse body areas, including deep-seated painful nodules, abscesses, draining sinus, and bridged scars, among others, with typical topography. To date, HS is considered a refractory disease and medical treatments aim to reduce the incidence, the infection, and the pain of the lesions. For this purpose, different classes of drugs, including anti-inflammatory molecules, antibiotics and biological drugs are being used. Antimicrobial peptides (AMPs), also called defense peptides, emerge as a new class of therapeutic compounds, with broad-spectrum antimicrobial action, in addition to reports on their anti-inflammatory, healing, and immunomodulating activity. Such peptides are present in prokaryotes and eukaryotes, as part of the innate eukaryotic immune system. It has been proposed that a deregulation in the expression of AMPs in human epithelial tissues of HS patients may be associated with the etiology of this skin disease. In this scenario, plant AMPs stand out for their richness, diversity of types, and broad antimicrobial effects, with potential application for topical systemic use in patients affected by HS.

scholarly journals Dysregulation of tryptophan catabolism at the host-skin microbiota interface in hidradenitis suppurativa

JCI Insight ◽  
2020 ◽  
Vol 5 (20) ◽  
Author(s):  
Laure Guenin-Macé ◽  
Jean-David Morel ◽  
Jean-Marc Doisne ◽  
Angèle Schiavo ◽  
Lysiane Boulet ◽  
...  
Keyword(s):  
Hidradenitis Suppurativa ◽  
Skin Microbiota ◽  
Tryptophan Catabolism

Chronic Skin Lesions in Type 2 Diabetic Subjects

2018 ◽  
Vol 18 ◽  
Author(s):  
Eleonora Margherita Chisari ◽  
Borzi Antonio Maria ◽  
Luca Salvatore ◽  
Chisari Giuseppe ◽  
Chisari Clara Grazia
Keyword(s):  
Skin Lesions ◽  
Chronic Skin ◽  
Type 2 Diabetic

scholarly journals MCPIP1/Regnase-1 Expression in Keratinocytes of Patients with Hidradenitis Suppurativa: Preliminary Results

2021 ◽  
Vol 22 (14) ◽  
pp. 7241
Author(s):  
Piotr K. Krajewski ◽  
Weronika Szukała ◽  
Agata Lichawska-Cieślar ◽  
Łukasz Matusiak ◽  
Jolanta Jura ◽  
...  
Keyword(s):  
Western Blot ◽  
Mrna Expression ◽  
Hidradenitis Suppurativa ◽  
Skin Lesions ◽  
Healthy Controls ◽  
Lesional Skin ◽  
Chemotactic Protein ◽  
Healthy Control ◽  
Mrna And Protein Expression ◽  
Skin Biopsies

The pathogenesis of hidradenitis suppurativa (HS) is yet to be fully understood. However, inflammation is a key element in the development of skin lesions. The aim of this study was to evaluate the expression of monocyte chemotactic protein-1-induced protein-1 (MCPIP1) in the skin of patients suffering from HS. Skin biopsies of 15 patients with HS and 15 healthy controls were obtained and processed for immunohistochemistry, western blot, and real time PCR. The highest mean MCPIP1 mRNA expression was found in the inflammatory lesional skin of HS patients. It was significantly higher than MCPIP1 mRNA expression in the biopsies from both healthy controls and non-lesional skin of HS patients. Western blot analysis indicated that expression of MCPIP1 was elevated within both lesional and non-lesional skin compared to the healthy control. The increased MCPIP1 mRNA and protein expression level in HS lesions may indicate its possible role in the disease pathogenesis.

scholarly journals Low Back Pain in Hidradenitis Suppurativa: A Diagnosis Not to Miss!

2018 ◽  
Vol 10 (2) ◽  
pp. 187-189
Author(s):  
Benjamin Schnebert ◽  
Véronique del Marmol ◽  
Farida Benhadou
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Hidradenitis Suppurativa ◽  
Combined Therapy ◽  
Skin Lesions ◽  
Skin Area ◽  
Low Back ◽  
Inflammatory Drugs ◽  
The Right ◽  
Altered Sensitivity

We report the case of a patient suffering from hidradenitis suppurativa since puberty and complaining of chronic low back pain associated to altered sensitivity and muscular weakness in the right leg. A diagnosis of lumbosciatica was confirmed. Symptoms were not relieved after the use of nonsteroidal anti-inflammatory drugs and analgesics. A surgical decompression was then indicated but heavily debated. Indeed, extended inflammatory and fibrotic hidradenitis suppurativa lesions were located regarding the skin area eligible for the proposed surgery. A combined therapy with clindamycine/rifampicin was started and the surgery was postponed. A complete remission of the articular symptoms was observed 1 month after the start of the antibiotherapy and the inflammatory skin lesions were greatly improved. With the presentation of this clinical case, we would like to discuss the spectrum of rheumatic disorders associated to hidradenitis suppurativa that needs to be correctly diagnosed and taken into consideration in the therapeutic management of the patient.

scholarly journals Lithium inhibits tryptophan catabolism via the inflammation-induced kynurenine pathway in human microglia

2020 ◽  
Author(s):  
Ria Göttert ◽  
Pawel Fidzinski ◽  
Larissa Kraus ◽  
Ulf Christoph Schneider ◽  
Martin Holtkamp ◽  
...  
Keyword(s):  
Chromatin Immunoprecipitation ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Kynurenine Pathway ◽  
Mrna Transcription ◽  
Human Microglia ◽  
Tryptophan Catabolism ◽  
Induced Pluripotent ◽  
Sb 216763 ◽  
Gsk3 Inhibitor

SummaryActivation of the kynurenine pathway may lead to depletion of the serotonin precursor tryptophan, which has been implicated in the neurobiology of depression. This study describes a mechanism whereby lithium inhibits inflammatory tryptophan breakdown. Upon activation, immortalized human microglia showed a robust increase in indoleamine-2,3-dioxygenase (IDO1) mRNA transcription, IDO1 protein expression, and activity. Further, chromatin immunoprecipitation verified enriched binding of both STAT1 and STAT3 to the IDO1 promoter. Lithium counteracted these effects, increasing inhibitory GSK3βS9 phosphorylation and reducing STAT1S727 and STAT3Y705 phosphorylation levels in activated cells. Experiments in primary human microglia and human induced pluripotent stem cell (hiPSC)-derived microglia corroborated lithium’s effects. Moreover, IDO activity was reduced by GSK3 inhibitor SB-216763 and STAT inhibitor nifuroxazide via downregulation of P-STAT1S727 and P-STAT3Y705. Our study demonstrates that lithium inhibits the inflammatory kynurenine pathway in the microglia compartment of the human brain.

scholarly journals Hidradenitis Suppurativa: “A surgical Update with Review of Literature”

2021 ◽  
pp. 1-4
Author(s):  
UwaisRiaz Ul Hasan ◽  
◽  
Farooq Qureishi ◽  
Khathija Hasan ◽  
Nidal Khraisat ◽  
...  
Keyword(s):  
Social Life ◽  
Hidradenitis Suppurativa ◽  
Skin Condition ◽  
The Body ◽  
Fistula Formation ◽  
Sweat Glands ◽  
Chronic Patients ◽  
Foul Smell ◽  
Chronic Skin ◽  
End Stage

Hidradenitis suppurativa (HS) is a chronic skin disease primarily affecting the sweat glands apocrine zone of the body and what starts initially as an abscess progresses to nodules, sinus tracts, with cicatrisation fistula formation and ulcers. It is common to see all the stages of clinical spectrum viz multiple solitary abscess to nodules with sinus, fistulas with ulceration and cicatrisation in chronic patients. This chronic illness takes a toll on the psyche of these individuals as the need to avoid foul smell and the constant need for dressing dictate their social life. The patients are notoriously know for follow up for years. A low self-esteem and depression are companions of hidradenitis suppurativa (HS) individuals. Early involvement of the surgeon can substantially improve the progress and evolution of this chronic skin condition and could obviate the development of SCC the end stage of all Chronic neglected Hidradenitis suppurativa (HS) cases especially in the hi risk older age group of individuals

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