» Articles » PMID: 16367938

Dose-dependent Induction of IL-6 by Plant-derived Proteases in Vitro

Overview
Date 2005 Dec 22
PMID 16367938
Citations 7
Authors
Affiliations
Soon will be listed here.
Abstract

Oral administration of proteases such as bromelain and papain is commonly used in patients with a wide range of inflammatory conditions, but their molecular and cellular mechanisms of action are still poorly understood. The aim of our study was to investigate the impact of these proteases on the release of interleukin-6 (IL-6) and other cytokines in the recently described modified mixed lymphocyte culture (MMLC) test system which is based on the mutual interaction of cells of the innate and adaptive immunity. Bromelain and papain enhanced IL-6 production dose-dependently up to 400-fold in MMLC before and up to 30-fold after neutralization of LPS content of proteases using polymyxin B, indicating that IL-6 induction by protease treatment was attributable to both protease action and LPS content of enzyme preparations. The production of IFNgamma and IL-10 was not altered by bromelain or papain, indicating a selective and differential immune activation. Both proteases impaired cytokine stability, cell proliferation and expression of cell surface molecules like CD14 only marginally, suggesting no impact of these mechanisms on protease-mediated cytokine release. These findings might provide the mechanistic rationale for the current use of proteases in wound healing and tissue regeneration since these processes depend on IL-6 induction.

Citing Articles

Enhancing extraction efficiency of carpaine in L. leaves: coupling acid-base extraction with surfactant-assisted micro-flotation.

Lam T, Tran A, Le Anh Phan T, Zitzmann F, Van Ho Phan N, Nguyen K RSC Adv. 2024; 14(39):28768-28778.

PMID: 39263437 PMC: 11388190. DOI: 10.1039/d4ra05132g.


A Case Study Using Papaya Leaf Extract to Reverse Chemotherapy-Induced Thrombocytopenia in a GBM Patient.

Koehler A, Rao R, Rothman Y, Gozal Y, Struve T, Alschuler L Integr Cancer Ther. 2022; 21:15347354211068417.

PMID: 34984951 PMC: 8753228. DOI: 10.1177/15347354211068417.


A Randomized Controlled Trial of the Efficacy of Systemic Enzymes and Probiotics in the Resolution of Post-COVID Fatigue.

Rathi A, Jadhav S, Shah N Medicines (Basel). 2021; 8(9).

PMID: 34564089 PMC: 8472462. DOI: 10.3390/medicines8090047.


Study of the Radiosensitizing and Radioprotective Efficacy of Bromelain (a Pineapple Extract): In Vitro and In Vivo.

Mekkawy M, Fahmy H, Nada A, Ali O Integr Cancer Ther. 2020; 19:1534735420950468.

PMID: 32783540 PMC: 7425266. DOI: 10.1177/1534735420950468.


Carica papaya induces in vitro thrombopoietic cytokines secretion by mesenchymal stem cells and haematopoietic cells.

Aziz J, Abu Kassim N, Abu Kasim N, Haque N, Rahman M BMC Complement Altern Med. 2015; 15:215.

PMID: 26152209 PMC: 4495848. DOI: 10.1186/s12906-015-0749-6.


References
1.
Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen B . IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest. 2004; 113(9):1271-6. PMC: 398432. DOI: 10.1172/JCI20945. View

2.
Nielsen H . Isolation and functional activity of human blood monocytes after adherence to plastic surfaces: comparison of different detachment methods. Acta Pathol Microbiol Immunol Scand C. 1987; 95(2):81-4. DOI: 10.1111/j.1699-0463.1987.tb00012.x. View

3.
Martin S, Maruta K, Burkart V, Gillis S, Kolb H . IL-1 and IFN-gamma increase vascular permeability. Immunology. 1988; 64(2):301-5. PMC: 1384958. View

4.
Desser L, Rehberger A . Induction of tumor necrosis factor in human peripheral-blood mononuclear cells by proteolytic enzymes. Oncology. 1990; 47(6):475-7. DOI: 10.1159/000226875. View

5.
Hale L, Haynes B . Bromelain treatment of human T cells removes CD44, CD45RA, E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 surface molecules and markedly enhances CD2-mediated T cell activation. J Immunol. 1992; 149(12):3809-16. View