scholarly journals Indoleamine 2,3-Dioxygenase 2 Deficiency Exacerbates Imiquimod-Induced Psoriasis-Like Skin Inflammation

2020 ◽  
Vol 21 (15) ◽  
pp. 5515
Author(s):  
Kento Fujii ◽  
Yasuko Yamamoto ◽  
Yoko Mizutani ◽  
Kuniaki Saito ◽  
Mariko Seishima
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Skin Inflammation ◽  
Kynurenine Pathway ◽  
Immune Functions ◽  
Wild Type ◽  
Indoleamine 2,3 Dioxygenase ◽  
Tnf Α ◽  
In The Wild

Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme known to suppress immune responses, and several reports have showed that it is associated with psoriasis. IDO2 is an isoform of IDO1, recently identified as a catalytic enzyme in the tryptophan-kynurenine pathway, which is expressed in dendritic cells and monocytes. The expression of IDO2 in immune cells suggests that IDO2 may contribute to immune functions. However, the role of IDO2 in the pathogenesis of psoriasis remains unclear. In this study, to elucidate the role of IDO2 in psoriasis, we assessed imiquimod (IMQ)-induced psoriasis-like dermatitis in IDO2 knockout (KO) mice. Skin inflammation, evaluated by scoring erythema, scaling, and ear thickness, was significantly worse in the IDO2 KO mice than in the wild-type (WT) mice. The mRNA expression levels of TNF-α, IL-23p19, and IL-17A, key cytokines involved in the development of psoriasis, were also increased in the IDO2 KO mice. Furthermore, immunohistochemistry revealed that the number of Ki67-positive cells in the epidermis and CD4-, CD8-, and IL-17-positive lymphocytes infiltrating the dermis were significantly increased in the IDO2 KO mice. These results suggest that IDO2 might decrease IL-17 expression, thereby resulting in the suppression of skin inflammation in IMQ-induced psoriasis-like dermatitis.

scholarly journals Transcriptome Changes in Pseudomonas putida KT2440 during Medium-Chain-Length Polyhydroxyalkanoate Synthesis Induced by Nitrogen Limitation

2020 ◽  
Vol 22 (1) ◽  
pp. 152
Author(s):  
Dorota Dabrowska ◽  
Justyna Mozejko-Ciesielska ◽  
Tomasz Pokój ◽  
Slawomir Ciesielski
Keyword(s):  
Chain Length ◽  
Nitrogen Limitation ◽  
Stringent Response ◽  
Wild Type ◽  
Pseudomonas Putida Kt2440 ◽  
Medium Chain ◽  
Environmental Stimuli ◽  
Medium Chain Length ◽  
In The Wild

Pseudomonas putida’s versatility and metabolic flexibility make it an ideal biotechnological platform for producing valuable chemicals, such as medium-chain-length polyhydroxyalkanoates (mcl-PHAs), which are considered the next generation bioplastics. This bacterium responds to environmental stimuli by rearranging its metabolism to improve its fitness and increase its chances of survival in harsh environments. Mcl-PHAs play an important role in central metabolism, serving as a reservoir of carbon and energy. Due to the complexity of mcl-PHAs’ metabolism, the manner in which P. putida changes its transcriptome to favor mcl-PHA synthesis in response to environmental stimuli remains unclear. Therefore, our objective was to investigate how the P. putida KT2440 wild type and mutants adjust their transcriptomes to synthesize mcl-PHAs in response to nitrogen limitation when supplied with sodium gluconate as an external carbon source. We found that, under nitrogen limitation, mcl-PHA accumulation is significantly lower in the mutant deficient in the stringent response than in the wild type or the rpoN mutant. Transcriptome analysis revealed that, under N-limiting conditions, 24 genes were downregulated and 21 were upregulated that were common to all three strains. Additionally, potential regulators of these genes were identified: the global anaerobic regulator (Anr, consisting of FnrA, Fnrb, and FnrC), NorR, NasT, the sigma54-dependent transcriptional regulator, and the dual component NtrB/NtrC regulator all appear to play important roles in transcriptome rearrangement under N-limiting conditions. The role of these regulators in mcl-PHA synthesis is discussed.

scholarly journals The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis

2021 ◽  
Vol 22 (13) ◽  
pp. 7227
Author(s):  
Lai-San Wong ◽  
Yu-Ta Yen ◽  
Chih-Hung Lee
Keyword(s):  
Atopic Dermatitis ◽  
Environmental Factors ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Disease ◽  
Targeted Therapies ◽  
Skin Barrier ◽  
Skin Barrier Function ◽  
Inflammatory Molecules

Atopic dermatitis (AD) is a prototypic inflammatory disease that presents with intense itching. The pathophysiology of AD is multifactorial, involving environmental factors, genetic susceptibility, skin barrier function, and immune responses. A recent understanding of pruritus transmission provides more information about the role of pruritogens in the pathogenesis of AD. There is evidence that pruritogens are not only responsible for eliciting pruritus, but also interact with immune cells and act as inflammatory mediators, which exacerbate the severity of AD. In this review, we discuss the interaction between pruritogens and inflammatory molecules and summarize the targeted therapies for AD.

scholarly journals Inflammasomes inMycobacterium tuberculosis-Driven Immunity

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Sebastian Wawrocki ◽  
Magdalena Druszczynska
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inflammatory Response ◽  
Immune Responses ◽  
Proinflammatory Cytokines ◽  
Immune Cells ◽  
Protein Complexes ◽  
Inflammasome Activation ◽  
Host Immune Responses ◽  
Multimeric Protein

The development of effective innate and subsequent adaptive host immune responses is highly dependent on the production of proinflammatory cytokines that increase the activity of immune cells. The key role in this process is played by inflammasomes, multimeric protein complexes serving as a platform for caspase-1, an enzyme responsible for proteolytic cleavage of IL-1βand IL-18 precursors. Inflammasome activation, which triggers the multifaceted activity of these two proinflammatory cytokines, is a prerequisite for developing an efficient inflammatory response against pathogenicMycobacterium tuberculosis(M.tb). This review focuses on the role of NLRP3 and AIM2 inflammasomes inM.tb-driven immunity.

Social Stressors, Arboviral Infection, and Immune Dysregulation in the Coastal Lowland Region of Ecuador: A Mixed Methods Approach in Ecological Perspective

2021 ◽  
Author(s):  
Denisse Vega Ocasio ◽  
Anna M. Stewart-Ibarra ◽  
Rachel Sippy ◽  
Christina Li ◽  
Kaitlyn McCue ◽  
...  
Keyword(s):  
At Risk ◽  
Immune Responses ◽  
Inflammatory Responses ◽  
Social Stressors ◽  
Biological Responses ◽  
Distress Symptoms ◽  
Tnf Α ◽  
Hair Samples ◽  
Arboviral Diseases

Aedes aegypti, the mosquito that transmits arboviral diseases such as dengue (DENV), chikungunya (CHIKV), and Zika viruses (ZIKV), is present in tropical and subtropical regions of the world. Individuals at risk of mosquito-borne disease (MBD) in the urban tropics face daily challenges linked to their socio-environment conditions, such as poor infrastructure, poverty, crowding, and limited access to adequate healthcare. These daily demands induce chronic stress events and dysregulated immune responses. We sought to investigate the role of socio-ecologic risk factors in distress symptoms and their impact on biological responses to MBD in Machala, Ecuador. Between 2017 and 2019, individuals (≥ 18 years) with suspected arbovirus illness (DENV, ZIKV, and CHIKV) from sentinel clinics were enrolled (index cases, N = 28). Cluster investigations of the index case households and people from four houses within a 200-m radius of index home (associate cases, N = 144) were conducted (total N = 172). Hair samples were collected to measure hair cortisol concentration (HCC) as a stress biomarker. Blood samples were collected to measure serum cytokines concentrations of IL-10, IL-8, TNF-α, and TGF-β. Univariate analyses were used to determine the association of socio-health metrics related to perceived stress scores (PSS), HCC, and immune responses. We found that housing conditions influence PSS and HCC levels in individuals at risk of MBD. Inflammatory cytokine distribution was associated with the restorative phase of immune responses in individuals with low-moderate HCC. These data suggest that cortisol may dampen pro-inflammatory responses and influence activation of the restorative phase of immune responses to arboviral infections.

scholarly journals Cytosolic Phospholipase A2α–deficient Mice Are Resistant to Collagen-induced Arthritis

2003 ◽  
Vol 197 (10) ◽  
pp. 1297-1302 ◽  
Author(s):  
Martin Hegen ◽  
Linhong Sun ◽  
Naonori Uozumi ◽  
Kazuhiko Kume ◽  
Mary E. Goad ◽  
...  
Keyword(s):  
Critical Role ◽  
Wild Type ◽  
Collagen Induced Arthritis ◽  
Cytosolic Phospholipase ◽  
Severity Scores ◽  
In The Wild ◽  
Cytosolic Phospholipase A2α ◽  
Antibody Levels ◽  
Deficient Mice

Pathogenic mechanisms relevant to rheumatoid arthritis occur in the mouse model of collagen-induced arthritis (CIA). Cytosolic phospholipase A2α (cPLA2α) releases arachidonic acid from cell membranes to initiate the production of prostaglandins and leukotrienes. These inflammatory mediators have been implicated in the development of CIA. To test the hypothesis that cPLA2α plays a key role in the development of CIA, we backcrossed cPLA2α-deficient mice on the DBA/1LacJ background that is susceptible to CIA. The disease severity scores and the incidence of disease were markedly reduced in cPLA2α-deficient mice compared with wild-type littermates. At completion of the study, >90% of the wild-type mice had developed disease whereas none of the cPLA2α-deficient mice had more than one digit inflamed. Furthermore, visual disease scores correlated with severity of disease determined histologically. Pannus formation, articular fibrillation, and ankylosis were all dramatically reduced in the cPLA2α-deficient mice. Although the disease scores differed significantly between cPLA2α mutant and wild-type mice, anti-collagen antibody levels were similar in the wild-type mice and mutant littermates. These data demonstrate the critical role of cPLA2α in the pathogenesis of CIA.

scholarly journals The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia

2021 ◽  
Author(s):  
Wai W Cheung ◽  
Ronghao Zheng ◽  
Sheng Hao ◽  
Zhen Wang ◽  
Alex Gonzalez ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Muscle Wasting ◽  
Differentially Expressed ◽  
Wild Type ◽  
Tnf Α ◽  
Fiber Size ◽  
Muscle Genes ◽  
Muscle Fat Infiltration

Abstract Cytokines such as IL-6, TNF-α and IL-1β trigger inflammatory cascades which may play a role in the pathogenesis of chronic kidney disease (CKD)-associated cachexia. CKD was induced by 5/6 nephrectomy in mice. We studied energy homeostasis in Il1β −/−/CKD, Il6−/−/CKD and Tnfα −/−/CKD mice and compared with wild type (WT)/CKD controls. Parameters of cachexia phenotype were completely normalized in Il1β −/−/CKD mice but were only partially rescued in Il6−/−/CKD and Tnfα −/−/CKD mice. We tested the effects of anakinra, an IL-1 receptor antagonist, on CKD-associated cachexia. WT/CKD mice were treated with anakinra (2.5 mg.kg.day, IP) or saline for 6 weeks and compared with WT/sham controls. Anakinra normalized food intake and weight gain, fat and lean mass content, metabolic rate and muscle function, and also attenuated molecular perturbations of energy homeostasis in adipose tissue and muscle in WT/CKD mice. Anakinra attenuated browning of white adipose tissue in WT/CKD mice. Moreover, anakinra normalized gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in WT/CKD mice. This was accompanied by correcting the increased muscle wasting signaling pathways while promoting the decreased myogenesis process in gastrocnemius of WT/CKD mice. We performed qPCR analysis for the top 20 differentially expressed muscle genes previously identified via RNAseq analysis in WT/CKD mice versus controls. Importantly, 17 differentially expressed muscle genes were attenuated in anakinra treated WT/CKD mice. In conclusion, IL-1 receptor antagonism may represent a novel targeted treatment for adipose tissue browning and muscle wasting in CKD.

scholarly journals Regulatory Immune Cells in Idiopathic Pulmonary Fibrosis: Friends or Foes?

2021 ◽  
Vol 12 ◽  
Author(s):  
Chiel van Geffen ◽  
Astrid Deißler ◽  
Markus Quante ◽  
Harald Renz ◽  
Dominik Hartl ◽  
...  
Keyword(s):  
Immune System ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Immune Responses ◽  
Immune Cells ◽  
Current Knowledge ◽  
Suppressor Cells ◽  
Interstitial Lung Diseases ◽  
Stromal Stem Cells

The immune system is receiving increasing attention for interstitial lung diseases, as knowledge on its role in fibrosis development and response to therapies is expanding. Uncontrolled immune responses and unbalanced injury-inflammation-repair processes drive the initiation and progression of idiopathic pulmonary fibrosis. The regulatory immune system plays important roles in controlling pathogenic immune responses, regulating inflammation and modulating the transition of inflammation to fibrosis. This review aims to summarize and critically discuss the current knowledge on the potential role of regulatory immune cells, including mesenchymal stromal/stem cells, regulatory T cells, regulatory B cells, macrophages, dendritic cells and myeloid-derived suppressor cells in idiopathic pulmonary fibrosis. Furthermore, we review the emerging role of regulatory immune cells in anti-fibrotic therapy and lung transplantation. A comprehensive understanding of immune regulation could pave the way towards new therapeutic or preventive approaches in idiopathic pulmonary fibrosis.

scholarly journals The Role of Vitamin D and Vitamin D Receptor in Immunity toLeishmania majorInfection

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
James P. Whitcomb ◽  
Mary DeAgostino ◽  
Mark Ballentine ◽  
Jun Fu ◽  
Martin Tenniswood ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune Responses ◽  
Vitamin D Receptor ◽  
Leishmania Major ◽  
Active Form ◽  
Wild Type ◽  
Vitamin D Signaling ◽  
Deficient Mice ◽  
Th 1

Vitamin D signaling modulates a variety of immune responses. Here, we assessed the role of vitamin D in immunity to experimental leishmaniasis infection in vitamin D receptor-deficient mice (VDRKO). We observed that VDRKO mice on a genetically resistant background have decreasedLeishmania major-induced lesion development compared to wild-type (WT) mice; additionally, parasite loads in infected dermis were significantly lower at the height of infection. Enzymatic depletion of the active form of vitamin D mimics the ablation of VDR resulting in an increased resistance toL. major. Conversely, VDRKO or vitamin D-deficient mice on the susceptible Th2-biased background had no change in susceptibility. These studies indicate vitamin D deficiency, either through the ablation of VDR or elimination of its ligand, 1,25D3, leads to an increase resistance toL. majorinfection but only in a host that is predisposed for Th-1 immune responses.

scholarly journals Role of Nitric Oxide in the Pathogenesis of Encephalomyocarditis Virus-Induced Diabetes in Mice

2009 ◽  
Vol 83 (16) ◽  
pp. 8004-8011 ◽  
Author(s):  
Young-Sun Lee ◽  
Na Li ◽  
Seungjin Shin ◽  
Hee-Sook Jun
Keyword(s):  
Virus Infection ◽  
Encephalomyocarditis Virus ◽  
Wild Type ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Diabetes In Mice ◽  
Tnf Α ◽  
Deficient Mice

ABSTRACT The D variant of encephalomyocarditis virus (EMC-D virus) causes diabetes in mice by destroying pancreatic β cells. In mice infected with a low dose of EMC-D virus, macrophages play an important role in β-cell destruction by producing soluble mediators such as interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), and nitric oxide (NO). To investigate the role of NO and inducible NO synthase (iNOS) in the development of diabetes in EMC-D virus-infected mice, we infected iNOS-deficient DBA/2 mice with EMC-D virus (2 × 102 PFU/mouse). Mean blood glucose levels in EMC-D virus-infected iNOS-deficient mice and wild-type mice were 205.5 and 466.7 mg/dl, respectively. Insulitis and macrophage infiltration were reduced in islets of iNOS-deficient mice compared with wild-type mice at 3 days after EMC-D virus infection. Apoptosis of β cells was decreased in iNOS-deficient mice, as evidenced by reduced numbers of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells. There were no differences in mRNA expression of antiapoptotic molecules Bcl-2, Bcl-xL, Bcl-w, Mcl-1, cIAP-1, and cIAP-2 between wild-type and iNOS-deficient mice, whereas expression of proapoptotic Bax and Bak mRNAs was significantly decreased in iNOS-deficient mice. Expression of IL-1β and TNF-α mRNAs was significantly decreased in both islets and macrophages of iNOS-deficient mice compared with wild-type mice after EMC-D virus infection. Nuclear factor κB was less activated in macrophages of iNOS-deficient mice after virus infection. We conclude that NO plays an important role in the activation of macrophages and apoptosis of pancreatic β cells in EMC-D virus-infected mice and that deficient iNOS gene expression inhibits macrophage activation and β-cell apoptosis, contributing to prevention of EMC-D virus-induced diabetes.

The development of the sensory neuron pattern in the antennal disc of wild-type and mutant (lz3, ssa) Drosophila melanogaster

Development ◽  
1991 ◽  
Vol 112 (4) ◽  
pp. 1063-1075
Author(s):  
M.C. Lienhard ◽  
R.F. Stocker
Keyword(s):  
Drosophila Melanogaster ◽  
Sensory Neuron ◽  
Antennal Segment ◽  
Wild Type ◽  
Homeotic Mutant ◽  
In The Wild ◽  
The Brain ◽  
Antennal Disc ◽  
Antennal Nerve

The development of the sensory neuron pattern in the antennal disc of Drosophila melanogaster was studied with a neuron-specific monoclonal antibody (22C10). In the wild type, the earliest neurons become visible 3 h after pupariation, much later than in other imaginal discs. They lie in the center of the disc and correspond to the neurons of the adult aristal sensillum. Their axons join the larval antennal nerve and seem to establish the first connection towards the brain. Later on, three clusters of neurons appear in the periphery of the disc. Two of them most likely give rise to the Johnston's organ in the second antennal segment. Neurons of the olfactory third antennal segment are formed only after eversion of the antennal disc (clusters t1-t3). The adult pattern of antennal neurons is established at about 27% of metamorphosis. In the mutant lozenge3 (lz3), which lacks basiconic antennal sensilla, cluster t3 fails to develop. This indicates that, in the wild type, a homogeneous group of basiconic sensilla is formed by cluster t3. The possible role of the lozenge gene in sensillar determination is discussed. The homeotic mutant spineless-aristapedia (ssa) transforms the arista into a leg-like tarsus. Unlike leg discs, neurons are missing in the larval antennal disc of ssa. However, the first neurons differentiate earlier than in normal antennal discs. Despite these changes, the pattern of afferents in the ectopic tarsus appears leg specific, whereas in the non-transformed antennal segments a normal antennal pattern is formed. This suggests that neither larval leg neurons nor early aristal neurons are essential for the outgrowth of subsequent afferents.

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