Bromelain Treatment Alters Leukocyte Expression of Cell Surface Molecules Involved in Cellular Adhesion and Activation

Hale, Laura P.; Greer, Paula K.; Sempowski, Gregory D.

doi:10.1006/clim.2002.5254

Cited by 98 publications

(106 citation statements)

References 33 publications

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“…the CD14 receptor for bacterial LPS on monocytes and the CD21 activation regulator on B cells; 16). Bromelain also removes cell surface receptors that can serve as receptors for intestinal bacteria (16,(37)(38)(39)(40)(41), which may decrease exposure of immune cells to bacterial antigens that stimulate detrimental immune responses in IBD. Proteolysis by bromelain may also affect production of pro-inflammatory cytokines and chemokines by altering concentrations of regulatory cytokines such as IL-10 or TGF-β that was not analyzed in the current study.…”

Section: Discussionmentioning

confidence: 99%

“…One biopsy of each set was treated with 1 mg/ml bromelain (catalog #B-4882; Sigma-Aldrich Chemical Co., St. Louis, MO) in RPMI + 1X pen/strep (media) for 1 hour at 37°C while the other was treated with media alone. These treatment conditions have previously been shown to be sufficient to remove bromelain-sensitive molecules from a variety of different cell types (15,16,21). All biopsies were treated using aliquots derived from the same lot of bromelain.…”

Section: Culture Of Colon Biopsies and Cytokine Assaysmentioning

confidence: 99%

“…We and others have previously shown that in vitro treatment with bromelain removes certain cell surface molecules that affect leukocyte migration and activation (15)(16)(17)(18). Treatment with proteolytically active bromelain affects T cell expression of mRNAs encoding IL-2, IL-4, and interferon (IFN)-γ and inhibits ERK-2-mediated signal transduction in leukocyte and colon epithelial cell lines in vitro (19,20).…”

Section: Introductionmentioning

confidence: 99%

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Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro

Onken

Greer

Calingaert

et al. 2008

Clinical Immunology

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Oral bromelain has been anecdotally reported to decrease inflammation in ulcerative colitis (UC). Proteolytically active bromelain is known to decrease expression of mRNAs encoding proinflammatory cytokines by human leukocytes in vitro. To assess the effect of bromelain on mucosal secretion of cytokines in inflammatory bowel disease (IBD), endoscopic colon biopsies from patients with UC, Crohn's disease (CD), and non-IBD controls were treated in vitro with bromelain or media, then cultured. Secretion of pro-inflammatory cytokines and chemokines was measured. Significant increases in granulocyte colony stimulating factor (G-CSF), interferon (IFN)-γ, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) were detected in the media from actively inflamed areas in UC and CD as compared with non-inflamed IBD tissue and non-IBD controls. In vitro bromelain treatment decreased secretion of G-CSF, granulocyte-macrophage colony stimulating factor (GM-CSF), IFN-γ, CCL4/macrophage inhibitory protein (MIP)-1β, and TNF by inflamed tissue in IBD. Bromelain may be a novel therapy for IBD.

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Section: Discussionmentioning

confidence: 99%

Section: Culture Of Colon Biopsies and Cytokine Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro

Onken

Greer

Calingaert

et al. 2008

Clinical Immunology

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“…Bromelain treatment has previously been shown to remove the CD128a/CXCR1 and CD128b/ CXCR2 receptors for IL-8, a chemokine that stimulates neutrophil chemotaxis and activation, from human neutrophils (22). Therefore, we determined the effect of bromelain treatment on IL-8-stimulated migration of human neutrophils using an in vitro chemotaxis assay.…”

Section: Bromelain Treatment Decreases Rhil-8-induced Migration Of Humentioning

confidence: 99%

“…However, proteolytic activity is required for the anti-inflammatory effect of bromelain on T cell activation and cytokine secretion in vitro (19)(20)(21) and in murine models of inflammatory bowel disease in vivo (17). We previously showed that in vitro bromelain treatment proteolytically removed at least 14 cell surface molecules that have been associated with leukocyte adhesion and/or activation (19,22). Among the bromelain-sensitive molecules identified were CD62L (L-selectin), CD128a (CXCR1) and CD128b (CXCR2).…”

Section: Introductionmentioning

confidence: 99%

Bromelain treatment decreases neutrophil migration to sites of inflammation

Fitzhugh

Shan

Dewhirst

et al. 2008

Clinical Immunology

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116

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Bromelain, a mixture of proteases derived from pineapple stem, has been reported to have therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease. The purpose of this work was to understand potential mechanisms for this anti-inflammatory activity. Exposure to bromelain in vitro has been shown to remove a number of cell surface molecules that are vital to leukocyte trafficking, including CD128a/CXCR1 and CD128b/CXCR2 that serve as receptors for the neutrophil chemoattractant IL-8 and its murine homologues. We hypothesized that specific proteolytic removal of CD128 molecules by bromelain would inhibit neutrophil migration to IL-8 and thus decrease acute responses to inflammatory stimuli. Using an in vitro chemotaxis assay, we demonstrated a 40% reduction in migration of bromelain-vs. sham-treated human neutrophils in response to rhIL-8. Migration to the bacterial peptide analog fMLP was unaffected, indicating that bromelain does not induce a global defect in leukocyte migration. In vivo bromelain treatment generated a 50 -85% reduction in neutrophil migration in 3 different murine models of leukocyte migration into the inflamed peritoneal cavity. Intravital microscopy demonstrated that although in vivo bromelain treatment transiently decreased leukocyte rolling, its primary long-term effect was abrogation of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in adhesion were correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin molecules that mediate rolling following in vivo bromelain treatment and minimal re-expression of CD128 over the time period studied. Taken together, these studies demonstrate that bromelain can effectively decrease neutrophil migration to sites of acute inflammation and support the specific removal of the CD128 chemokine receptor as a potential mechanism of action.

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Tacorin, an extract from Ananas comosus stem, stimulates wound healing by modulating the expression of tumor necrosis factor α, transforming growth factor β and matrix metalloproteinase 2

Rahayu¹,

Agustina²,

Tjandrawinata³

2017

FEBS Open Bio

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Wound healing is a complex biological process that involves integration of hemostasis, inflammation, proliferation and tissue remodeling. An extract of pineapple ( Ananas comosus ) stem demonstrates several therapeutics properties, including acceleration of wound healing. Tacorin is a water crude extract derived from the stem of A. comosus with high protein content. The effect of tacorin on wound healing in vivo was examined using rats with an induced injury. Wound closure was faster with tacorin treatment than in the untreated group. An in vitro study was conducted on mammalian cells (3T3‐L1) to observe the effect of tacorin on cell proliferation. Tacorin was first heated to inactivate its proteolytic activity. It increased the viability of 3T3‐L1 cells in a dose‐dependent manner. Excessive inflammation was suppressed by tacorin as shown by decreased tumor necrosis factor α expression. Treatment with tacorin increased the expression of transforming growth factor β, a major player in tissue remodeling. Moreover, tacorin also reduced the expression of MMP‐2 to accelerate the recovery of the wound. Taken together, tacorin is able to accelerate the wound‐healing process by increasing cell proliferation, suppressing inflammation and accelerating tissue remodeling.

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Bromelain Treatment Alters Leukocyte Expression of Cell Surface Molecules Involved in Cellular Adhesion and Activation

Cited by 98 publications

References 33 publications

Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro

Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro

Bromelain treatment decreases neutrophil migration to sites of inflammation

Tacorin, an extract from Ananas comosus stem, stimulates wound healing by modulating the expression of tumor necrosis factor α, transforming growth factor β and matrix metalloproteinase 2

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