In Vitro Therapeutic Effect of Epigallocatechin Gallate on Nicotine‐Induced Impairment of Resistance to<i>Legionella pneumophila</i>Infection of Established MH‐S Alveolar Macrophages

Matsunaga, Kazuto; Klein, Thomas; Friedman, Herman; Yamamoto, Yoshimasa

doi:10.1086/338449

Cited by 20 publications

(13 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4A to E). These data were compatible with the results of previous studies that had used other types of macrophages and other wild-type strains (1,9,15,23,30,66,67,69,75,80,87,103,120). In the case of IL-6, IL-8, and IL-10, expression levels above those of uninfected controls were evident at 24 h, whereas for TNF-␣ and IL-1␤, the effect of L. pneumophila was more easily seen at 48 h. Except with IL-10, elevated levels of expression were maintained until the end of the experiment at 72 h. Among the different cytokines, IL-8 showed the highest levels in the infected culture supernatants.…”

Section: Vol 79 2011supporting

confidence: 92%

Legionella pneumophila Type II Secretion Dampens the Cytokine Response of Infected Macrophages and Epithelia

et al. 2011

View full text Add to dashboard Cite

The type II secretion (T2S) system of Legionella pneumophila is required for the ability of the bacterium to grow within the lungs of A/J mice. By utilizing mutants lacking T2S (lsp), we now document that T2S promotes the intracellular infection of both multiple types of macrophages and lung epithelia. Following infection of macrophages, lsp mutants (but not a complemented mutant) elicited significantly higher levels of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-␣), IL-10, IL-8, IL-1␤, and MCP-1 within tissue culture supernatants. A similar result was obtained with infected lung epithelial cell lines and the lungs of infected A/J mice. Infection with a mutant specifically lacking the T2S-dependent ProA protease (but not a complemented proA mutant) resulted in partial elevation of cytokine levels. These data demonstrate that the T2S system of L. pneumophila dampens the cytokine/chemokine output of infected host cells. Upon quantitative reverse transcription (RT)-PCR analysis of infected host cells, an lspF mutant, but not the proA mutant, produced significantly higher levels of cytokine transcripts, implying that some T2S-dependent effectors dampen signal transduction and transcription but that others, such as ProA, act at a posttranscriptional step in cytokine expression. In summary, the impact of T2S on lung infection is a combination of at least three factors: the promotion of growth in macrophages, the facilitation of growth in epithelia, and the dampening of the chemokine and cytokine output from infected host cells. To our knowledge, these data are the first to identify a link between a T2S system and the modulation of immune factors following intracellular infection.The aquatic bacterium Legionella pneumophila is the primary agent of Legionnaires' disease, a potentially fatal form of pneumonia (38). L. pneumophila is especially pathogenic for the immunocompromised, the elderly, and smokers. Recent studies highlight the significance of travel-associated Legionnaires' disease and an increasing incidence of legionellosis (79). In natural and man-made waters, Gram-negative L. pneumophila survives planktonically, in biofilms, and as an intracellular parasite of protozoa (115). Infection occurs after the inhalation of contaminated droplets that originate from a variety of aerosol-generating devices as well as potable waters (33, 86). In the lung, L. pneumophila multiplies in resident alveolar macrophages, although persistence might also involve growth in alveolar epithelia and extracellular survival (82). Much of the pathogenesis and ecology of L. pneumophila is mediated by secreted factors, including protein and nonprotein molecules (2,25,27,44,57). For secreting proteins into the extracellular milieu and/or target host cells, L. pneumophila uses both the type II secretion (T2S) and the type IV secretion (T4S) system, large membrane-spanning apparatuses that are each composed of at least 10 component proteins (27,82).T2S promotes the physiology and ecology of many bacteria as well as the virulence o...

show abstract

Section: Vol 79 2011supporting

confidence: 92%

Legionella pneumophila Type II Secretion Dampens the Cytokine Response of Infected Macrophages and Epithelia

et al. 2011

View full text Add to dashboard Cite

show abstract

“…There was a significant interaction between LPS administration and GTP supplementation in TNF-α expression intensity osteoblasts [29]. Furthermore, studies also suggest that green tea bioactive components may modulate osteoimmunological activity (a) to inhibit differentiation of osteoclasts through the receptor activator of nuclear factor-κB ligand signaling pathway [30] or c-Jun N-terminal kinase (JNK)/cJun signaling pathways [31], and (b) to suppress the production of cytokines by immune cells [32].…”

Section: Discussionmentioning

confidence: 99%

Green tea polyphenols attenuate deterioration of bone microarchitecture in female rats with systemic chronic inflammation

et al. 2010

View full text Add to dashboard Cite

show abstract

“…This was shown in EGCG treatment of nicotine-suppressed macrophages where it reconstituted the resistance to the infection and diminished a nicotine-induced inhibition of cytokine production [468]. It was also demonstrated in research against Pseudomonas aeruginosa and Escherichia coli isolated from skin wounds [469], and against burn wound infection by methicillin-resistant Staphylococcus aureus [470].…”

Section: Low Toxicity Approachesmentioning

confidence: 98%

A multi-targeted approach to suppress tumor-promoting inflammation

Samadi

Bilsland

Georgakilas

et al. 2015

Seminars in Cancer Biology

View full text Add to dashboard Cite

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-kappaB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes.

show abstract

In Vitro Therapeutic Effect of Epigallocatechin Gallate on Nicotine‐Induced Impairment of Resistance toLegionella pneumophilaInfection of Established MH‐S Alveolar Macrophages

Cited by 20 publications

References 56 publications

Legionella pneumophila Type II Secretion Dampens the Cytokine Response of Infected Macrophages and Epithelia

Legionella pneumophila Type II Secretion Dampens the Cytokine Response of Infected Macrophages and Epithelia

Green tea polyphenols attenuate deterioration of bone microarchitecture in female rats with systemic chronic inflammation

A multi-targeted approach to suppress tumor-promoting inflammation

Contact Info

Product

Resources

About