Cytokines Expressed in the Granulomatous Lesions in Experimental Paracoccidioidomycosis: Role in Host Protective Immunity and as Fungal Virulence Factor

Burger, Eva; Nishikaku, Angela Satie; Gameiro, Jacy; Francelin, Carolina; Camargo, Zoilo Pires de; Verinaud, Liana

doi:10.4172/2155-9899.s1-010

Cited by 5 publications

(4 citation statements)

References 25 publications

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“…The study of the in situ expression of cytokines in PCM granulomas allowed a better comprehension of the interaction of P. brasiliensis with the immune system at the granulomas is important. Burger et al [ 13 ] associated the morphology of granulomas developed with the local synthesis of different cytokines. They showed that resistant mice that have compact granulomas develop a Th1-type response, with the presence of IFN-γ e TNF-α.…”

Section: Discussionmentioning

confidence: 99%

An improved high-performance liquid chromatography (HPLC) method for detection of variations in the hydroxyproline content of tissue homogenates from Paracoccidioides brasiliensis-infected mice

Gidlund,

Molina,

Burger

2024

J. Venom. Anim. Toxins incl. Trop. Dis

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Background: Paracoccidioidomycosis (PCM) is a severe granulomatous disease . The hallmark of this mycosis is fibrin degradation and granuloma formation as a result of a wound-healing process in the context of excessive inflammation. Therefore, as the content of collagen can be assessed by the methodology described in this manuscript, we propose that the content of hydroxyproline (HYP) be employed as a new and efficient measurement of granulomatous lesions developed. To estimate the level of HYP the major byproduct of the degradation process, we hypothesized that this simple and efficient technique could serve as a marker of disease severity. Methods: Five B10.A female mice were infected with P . brasiliensis and, after 15 days, the omentum was removed, subjected to histopathological analysis or processed (i.e. deproteinized and derivatized), and further analyzed on a reverse phase HPLC using a C-18 column. The omentum of five uninfected controls was also collected and similarly analyzed. Results: Infected mice showed numerous, disseminated paracoccidioidomycotic lesions, as well as marked collagen deposits, as observed in histopathologic analysis, and high levels of HYP. Normal uninfected mice showed no granulomas, little or no deposits of collagen fibers, and very low levels of HYP, as evaluated by HPLC. Our results show that the disease intensity as evaluated number and the morphology of the granulomatous lesions were correlated to the HYP levels using small tissue samples from the omentum, the main target organ of P. brasiliensis . Conclusions: Here we propose an alternative methodology to follow disease evolution and, to some extent, fungal load in experimental P. brasiliensis infection and suggest its usefulness to other diseases with pronounced fibrin degradation.

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Section: Discussionmentioning

confidence: 99%

An improved high-performance liquid chromatography (HPLC) method for detection of variations in the hydroxyproline content of tissue homogenates from Paracoccidioides brasiliensis-infected mice

Gidlund,

Molina,

Burger

2024

J. Venom. Anim. Toxins incl. Trop. Dis

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“…Our findings showed that naloxone decreased proinflammatory cytokine concentration including IL-1β and VEGF which cause joint injury by inducing recruitment of white blood cells, exudation and angiogenesis at the site of inflammation in rat model of arthritis. The cytokines derived from macrophages, such as TNF-α and IL-1, play a crucial role in the formation of granulation tissue, so that these cytokines are also called granulomatogenic cytokines (28). The inhibitory effects on the concentration of TNF-α and IL-1 (29,30) can be the proposed mechanisms to reduce the weight of granulation tissue by naloxone.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of anti-inflammatory and anti-angiogenesis effects of naloxone in the rat air pouch model of inflammation

Eteraf-Oskouei¹,

Zabiholahi²,

Najafi³

et al. 2020

Electron. physician

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Background and objective: There is increasing evidence that the nervous system is in two-way interaction with the immune system. To study the relationship between the opioid and immune systems, the anti-inflammatory effect of naloxone -an opioid receptor antagonist -in the air pouch model as an animal model of rheumatoid arthritis was studied. Methods: Sterile air (20 and 10 ml) was subcutaneously injected into the back of the animals on days 1 and 3, respectively. On the 6 th day, carrageenan was injected into the pouch. Normal saline and different doses of naloxone were injected immediately, as well as 24 and 48 hours after carrageenan in the control and treatment groups, respectively. After 72 hours, granulation tissue was opened, the pouch fluid was collected to determine the volume of exudates, the concentration of Vascular Endothelial Growth Factor (VEGF) and Interleukin 1 beta (IL-1β) and count of leukocyte. Granulation tissue was extruded and weighed. To assay the angiogenesis, the granulation tissue was homogenized and centrifuged, and the supernatant was filtered by a 0.22µ filter. Hemoglobin concentration was determined by the hemoglobin kit. Results: Naloxone clearly reduced leukocyte accumulation (p<0.01), exudate volume (p<0.001), granulation tissue weight (p<0.01), and amount of angiogenesis in the granulation tissue (p<0.001). In addition, VEGF and IL-1β levels were decreased significantly (p<0.01) and (p<0.001), respectively. Conclusion: Naloxone can reduce inflammatory and angiogenesis parameters in an air pouch inflammatory model. The anti-inflammatory effect is probably related to inhibition of leukocyte accumulation due to decreased concentration of inflammatory cytokines in exudates.

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“…Paracoccidioides spp. are able to induce the modulation of a chronic inflammatory response via the nitric oxide pathway and to exert a negative modulatory effect on granuloma formation in PCM (33,34). We evaluated the in vitro effect of G14 on nitric oxide modulation in RAW 264.7 macrophages infected with P. lutzii.…”

Section: Discussionmentioning

confidence: 99%

Decyl Gallate as a Possible Inhibitor of N-Glycosylation Process in Paracoccidioides lutzii

Silva

Oliveira

Scorzoni

et al. 2019

Antimicrob Agents Chemother

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The available antifungal therapeutic arsenal is limited. The search for alternative drugs with fewer side effects and new targets remains a major challenge. Decyl gallate (G14) is a derivative of gallic acid with a range of biological activities and broad-spectrum antifungal activity. Previously, our group demonstrated the promising anti-Paracoccidioides activity of G14. In this work, to evaluate the antifungal characteristics of G14 for Paracoccidioides lutzii, a chemical-genetic interaction analysis was conducted on a Saccharomyces cerevisiae model. N-glycosylation and/or the unfolded protein response pathway was identified as a high-confidence process for drug target prediction. The overactivation of unfolded protein response (UPR) signaling was confirmed using this model with IRE1/ATF6/PERK genes tagged with green fluorescent protein (GFP). In P. lutzii, this prediction was confirmed by the low activity of glycosylated enzymes [α-(1,3)-glucanase, N-acetyl-β-d-glucosaminidase (NAGase), and α-(1,4)-amylase], by hyperexpression of genes involved with the UPR and glycosylated enzymes, and by the reduction in the amounts of glycosylated proteins and chitin. All of these components are involved in fungal cell wall integrity and are dependent on the N-glycosylation process. This loss of integrity was confirmed by the reduction in mitochondrial activity, impaired budding, enhancement of wall permeability, and a decrease in viability. These events led to a reduction of the ability of fungi to adhere on human lung epithelial cells (A549) in vitro. Therefore, G14 may have an important role in balancing the inflammatory reaction caused by fungal infection, without interfering with the microbicidal activity of nitric oxide. This work provides new information on the activity of G14, a potential anti-Paracoccidioides compound.

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Cytokines Expressed in the Granulomatous Lesions in Experimental Paracoccidioidomycosis: Role in Host Protective Immunity and as Fungal Virulence Factor

Cited by 5 publications

References 25 publications

An improved high-performance liquid chromatography (HPLC) method for detection of variations in the hydroxyproline content of tissue homogenates from Paracoccidioides brasiliensis-infected mice

An improved high-performance liquid chromatography (HPLC) method for detection of variations in the hydroxyproline content of tissue homogenates from Paracoccidioides brasiliensis-infected mice

Evaluation of anti-inflammatory and anti-angiogenesis effects of naloxone in the rat air pouch model of inflammation

Decyl Gallate as a Possible Inhibitor of N-Glycosylation Process in Paracoccidioides lutzii

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