Role of porin ofShigella dysenteriaetype 1 in modulation of lipopolysaccharide mediated nitric oxide and interleukin-1 release by murine peritoneal macrophages

Introduction: An earlier constructed recombinant BCG expressing the MSP-1C of Plasmodium falciparum, induced inflammatory responses leading to significant production of nitric oxide (NO) alongside higher expression of the enzyme inducible nitric oxide synthase (iNOS) and significant production of the regulatory cytokine, IL-10, indicating significant immunomodulatory effects of the construct. The mechanism of these responses had not been established but is thought to involve toll-like receptor 4 (TLR-4). Methodology: The present study was carried out to determine the role of TLR-4 on eliciting the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum leading to the production of NO and IL-10, as well as the expression of iNOS. Six groups of mice (n = 6 per group) were immunised thrice, three weeks apart with intraperitoneal phosphate buffered saline T80 (PBS-T80), BCG or rBCG in the presence or absence of a TLR-4 inhibitor; TAK-242, given one hour prior to each immunisation. Peritoneal macrophages were harvested from the mice and cultured for the determination of NO, iNOS and IL-10 via Griess assay, ELISA and Western blot respectively. Results: The results showed significant inhibition of the production of NO and IL-10 and the expression of iNOS in all groups of mice in the presence of TAK-242. Conclusions: These results presented evidence of the role of TLR-4/rBCG attachment mechanism in modulating the production of NO and IL-10 and the expression of iNOS in response to our rBCG-based malaria vaccine candidate expressing MSP-1C of P. falciparum.

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Identification of Ellagic Acid Derivatives in Methanolic Extracts from Qualea Species

Zeitschrift für Naturforschung C ◽

10.1515/znc-2008-11-1203 ◽

2008 ◽

Vol 63 (11-12) ◽

pp. 794-800 ◽

Cited By ~ 9

Author(s):

Ana L. M. Nasser ◽

Camila B. A. Carli ◽

Clenilson M. Rodrigues ◽

Danielle C. G. Maia ◽

Iracilda Z. Carlos ◽

...

Keyword(s):

Nitric Oxide ◽

High Pressure ◽

Ellagic Acid ◽

Methanolic Extract ◽

Peritoneal Macrophages ◽

Biological Assays ◽

Methanolic Extracts ◽

Gel Permeation ◽

Murine Peritoneal Macrophages ◽

Lower Capacity

Abstract The methanolic extract from the barks of the medicinal plant Qualea parviflora (Vochysiaceae) was fractionated by column chromatography over silica gel followed by gel permeation over Sephadex LH-20 to give 3,3′-di-O-methylellagic acid-4-O-β-d-glucopyranoside (1), 3-Omethylellagic acid-4′-O-α-l-rhamnopyranoside (2), 3,3′,4-tri-O-methylellagic acid-4′-O-β-dglucopyranoside (3), and 3,3′-di-O-methylellagic acid (4), together with triterpenes and saponins. We also performed comparative analyses among this species and Q. grandiflora and Q. multiflora using high-pressure liquid chromatography. The biological assays showed that, when compared to the standard ellagic acid, compounds 1-4 are less cytotoxic but have a lower capacity of stimulating murine peritoneal macrophages to release nitric oxide and tumoural-α necrose factor.

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