Featured Article: Immunomodulatory effect of hemozoin on pneumocyte apoptosis viaCARD9pathway, a possibly retarding pulmonary resolution

Abstract

Plasmodium falciparum, the most virulent malaria parasite species, causes severe symptoms especially acute lung injury (ALI), of which characterized by alveolar epithelium and endothelium destruction and accelerated to blood-gas-barrier breakdown. Parasitized erythrocytes, endothelial cells, monocytes, and cytokines are all involved in this mechanism, but hemozoin (HZ), the parasitic waste from heme detoxification, also mainly contributes. In addition, it is not clear why type II pneumocyte proliferation, alveolar restorative stage, is rare in malaria-associated ALI. To address this, in vitro culture of A549 cells with Plasmodium HZ or with interleukin (IL)-1β triggered by HZ and monocytes (HZ-IL-1β) was conducted to determine their alveolar apoptotic effect using ethidium bromide/acridine orange staining, annexin-V-FITC/propidium iodide staining, and electron mircroscopic study. Caspase recruitment domain-containing protein 9 ( CARD9), the apoptotic regulator gene, and IL-1β were quantified by reverse-transcriptase PCR. Junctional cellular defects were characterized by immunohistochemical staining of E-cadherin. The results revealed that cellular apoptosis and CARD9 expression levels were extremely high 24 h after induction by HZ-IL-1β when compared to the HZ- and non-treated groups. E-cadherin was markedly down-regulated by HZ-IL-1β and HZ treatments. CARD9 expression was positively correlated with IL-1β expression and the number of apoptotic cells. Interestingly, the localization of HZ in the vesicular surfactant of apoptotic pneumocyte was also identified and submitted to be a cause of alveolar resolution abnormality. Thus, HZ triggers monocytes to produce IL-1β and induces pneumocyte type II apoptosis through CARD9 pathway in association with down-regulated E-cadherin, which probably impairs alveolar resolution in malaria-associated ALI. Impact statement The present work shows the physical and immunomodulatory properties of hemozoin on the induction of pneumocyte apoptosis in relation to IL-1β production through the CARD9 pathway. This occurrence may be a possible pathway for the retardation of lung resolution leading to blood-gas-barrier breakdown. Our findings lead to the understanding of the host-parasite relationship focusing on the dysfunction in ALI induced by HZ, a possible pathway of the recovering lung epithelial retardation in malaria-associated ARDS.

Malaria pigment accelerates MTT – formazan exocytosis in human endothelial cells

“…It has been described that HZ can induce apoptosis in type II pneumocytes and erythroid precursors and can interfere with cell cycle progression of erythroid cells (Lamikanra et al ., 2009; Skorokhod et al ., 2010; Maknitikul et al ., 2018). However, here we show that HZ did not induce apoptosis or modification of the cell cycle in endothelial cells, indicating that HZ can induce different effects depending on the cell type.…”

Evaluating the effect of rice (Oryza sativa L.: SRNC05053-6-2) crude extract on psoriasis using in vitro and in vivo models

“…To demonstrate the resolutive, antioxidative and immunomodulatory properties of the extract on both artificial and rat psoriasis skin specimens, the immunostaining, as described in our recent studies 30 – 35 , 38 , 39 , of caspase-3, nuclear factor erythroid 2-related factor (Nrf)-2, interleukin (IL)-10, TGF-β, β-defensin and CCL-20 were performed using rabbit isotype polyclonal antibodies (MyBioSource, USA). After deparaffinisation and dehydration, the antigenicity of the section was enhanced using heated citrate buffer (pH 6.0).…”

Streptozotocin induces alpha-2u globulin nephropathy in male rats during diabetic kidney disease

“…These sections were then stained with haematoxylin and eosin (H&E) and examined under a light microscope, focusing on (i) intracytoplasmic hyaline droplet deposition, tubular cast formation, tubular degeneration, tubular regeneration and Bowman's space distension with proteinaceous uid deposition for kidney, (ii) pyknotic nuclei, lymphocyte in ltration and centrilobular microvesicular steatosis for liver and (iii) Islet of Langerhans degeneration, vacuolar degeneration in the acinar gland and interstitial cell necrosis and in ammation of the pancreas. The lesions were semi-quantitatively graded using H-score (distribution [~0-100%/section] × severity score [0-3: 0 = absent, 1 = mild, 2 = moderate and 3 = severe]) as shown in our previous studies [39][40][41][42][43].…”