NLRP3 Inflammasome Activation in THP-1 Target Cells Triggered by Pathogenic Naegleria fowleri
| Autor: | Sun Park, Gi-Sang Seong, Hae-Jin Sohn, Kyongmin Kim, Heekyoung Kang, Jong-Kyun Yoo, Ho-Joon Shin, Yong-Joon Chwae, Jong-Hyun Kim |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Inflammasomes Interleukin-1beta 030106 microbiology Immunology Caspase 1 Inflammation Biology Microbiology Cathepsin B Amino Acid Chloromethyl Ketones 03 medical and health sciences Cell Line Tumor parasitic diseases Glyburide NLR Family Pyrin Domain-Containing 3 Protein medicine Humans THP1 cell line Naegleria fowleri Macrophages Inflammasome Dipeptides biology.organism_classification 030104 developmental biology Infectious Diseases Cell culture Parasitology Fungal and Parasitic Infections medicine.symptom Inflammasome complex medicine.drug |
| Zdroj: | Infection and Immunity. 84:2422-2428 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00275-16 |
| Popis: | Naegleria fowleri , known as the brain-eating amoeba, causes acute primary amoebic meningoencephalitis. During swimming and other recreational water activities, N. fowleri trophozoites penetrate the nasal mucosa and invade the olfactory bulbs, resulting in intense inflammatory reactions in the forebrain tissue. To investigate what kinds of inflammasome molecules are expressed in target cells due to N. fowleri infection, human macrophage cells (THP-1 cells) were cocultured with N. fowleri trophozoites in a noncontact system, and consequently, interleukin-1β (IL-1β) production was estimated. Caspase-1 activation and IL-1β production from THP-1 cells by Western blotting and the culture supernatant by enzyme-linked immunosorbent assay analysis were observed at 3 h after cocultivation. In addition, the increased expression of ASC and NLRP3, which make up an inflammasome complex, was also observed at 3 h after cocultivation. To confirm the caspase-1 activation and IL-1β production via the NLRP3 inflammasome in THP-1 cells triggered by N. fowleri trophozoites, THP-1 cells were pretreated with several inhibitors. The inhibition assay showed that CA-074 (a cathepsin B inhibitor), glybenclamide (an NLRP3 molecule inhibitor), and N -benzyloxycarbony-Val-Ala-Asp( O -methyl)-fluoromethylketone (Z-VAD-FMK; a caspase-1 inhibitor) reduced the levels of caspase-1 activation and IL-1β production from THP-1 cells. This study suggests that N. fowleri infection induces the NLRP3 inflammasome, which activates caspase-1 and subsequently produces IL-1β, thus resulting in inflammation. |
| Databáze: | OpenAIRE |
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