C-36 peptide, a degradation product of α1-antitrypsin, modulates human monocyte activation through LPS signaling pathways

Subramaniyam, Devipriya; Glader, Pernilla; Wachenfeldt, Karin von; Burneckiene, Jurate; Stevens, Tim; Janciauskiene, Sabina

doi:10.1016/j.biocel.2005.09.021

Cited by 37 publications

(34 citation statements)

References 47 publications

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“…SAA and a-1-antitrypsin are also present [124]. The finding of a-1-antitrypsin associated with HDL supported the possible role of HDL in innate immunity as a-1-antitrypsin is known to modulate activated neutrophils [125].…”

Section: Hdl Proteomicsmentioning

confidence: 85%

HDL functionality

Soran

Hama

Yadav

et al. 2012

Current Opinion in Lipidology

126

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Section: Hdl Proteomicsmentioning

confidence: 85%

HDL functionality

Soran

Hama

Yadav

et al. 2012

Current Opinion in Lipidology

126

View full text Add to dashboard Cite

“…4E). The C-terminal domain of ␣ 1 PI, like LPS, stimulates monocytes via CD14 and TLR4 (19). Stimulation of the plus and minus clones by either ␣ 1 PI or LPS induced phosphorylation of NF-B p65 Ser-536 equivalently (Fig.…”

Section: Ab Array and Phospho-epitope Analysismentioning

confidence: 90%

NF-κB Signaling, Elastase Localization, and Phagocytosis Differ in HIV-1 Permissive and Nonpermissive U937 Clones

Bristow

Wolkowicz

Trucy³

et al. 2008

The Journal of Immunology

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To identify positive or negative factors for HIV-1 infectivity, clones from the U937 promonocytic cell line that express similar levels of CD4 and CXCR4, but differ in HIV-1 susceptibility, were compared. In contrast to HIV-1 permissive clone 10 (plus), nonpermissive clone 17 (minus) was adherent to coverslips coated with chemokines, was phagocytic, killed bacteria, and expressed human leukocyte elastase (HLE) in a granule-like compartment (HLEG) that was never detected at the cell surface (HLECS). In contrast to the minus clone, the plus clone expressed HLE on the cell surface and was adherent to coverslips coated with the HLECS ligands α1proteinase inhibitor (α1PI, α1antitrypsin) and the HIV-1 fusion peptide. The phosphorylation status of several important signaling proteins was studied at the single cell level. Tumor suppressor p53, NF-κB p65, and Akt were constitutively phosphorylated in the plus clone, but not in the minus clone. Surprisingly, both α1PI and LPS induced phosphorylation of NF-κB p65 Ser-536 in both clones, but induced dephosphorylation of Ser-529 in the plus clone only. HIV-1 permissivity was conferred to the minus clone in a manner that required stimulation by both α1PI and LPS and was coincident to NF-κB p65 phosphorylation/dephosphorylation events as well as translocation of HLE to the cell surface. Even when stimulated, the minus clone exhibited greater reverse transcriptase activity, but less p24, than the plus clone. Results presented suggest that HIV-1 uptake and production efficiency are influenced by signaling profiles, receptor distribution, and the phagocytic capacity specific to the stage of differentiation of the CD4+ target cell.

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“…These five amino acids are located within a 36-amino acid C-terminal stretch, spanning amino acids 359-394. The so-called C-36 peptide was shown to attract neutrophils (27), as well as activate monocytes (28,29) and display atherogenic properties (30,31). The sequence is highly conserved among SERPINs and, intriguingly, is also mostly hydrophobic.…”

Section: Molecular Profile Of Aatmentioning

confidence: 99%

Expanding the Clinical Indications for α1-Antitrypsin Therapy

Lewis

2012

Mol Med

147

115

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α 1 -Antitrypsin (AAT) is a 52-kDa circulating serine protease inhibitor. Production of AAT by the liver maintains 0.9-1.75 mg/mL circulating levels. During acute-phase responses, circulating AAT levels increase more than fourfold. In individuals with one of several inherited mutations in AAT, low circulating levels increase the risk for lung, liver and pancreatic destructive diseases, particularly emphysema. These individuals are treated with lifelong weekly infusions of human plasma-derived AAT. An increasing amount of evidence appears to suggest that AAT possesses not only the ability to inhibit serine proteases, such as elastase and proteinase-3 (PR-3), but also to exert antiinflammatory and tissue-protective effects independent of protease inhibition. AAT modifies dendritic cell maturation and promotes T regulatory cell differentiation, induces interleukin (IL)-1 receptor antagonist and IL-10 release, protects various cell types from cell death, inhibits caspases-1 and -3 activity and inhibits IL-1 production and activity. Importantly, unlike classic immunosuppressants, AAT allows undeterred isolated T-lymphocyte responses. On the basis of preclinical and clinical studies, AAT therapy for nondeficient individuals may interfere with disease progression in type 1 and type 2 diabetes, acute myocardial infarction, rheumatoid arthritis, inflammatory bowel disease, cystic fibrosis, transplant rejection, graft versus host disease and multiple sclerosis. AAT also appears to be antibacterial and an inhibitor of viral infections, such as influenza and human immunodeficiency virus (HIV), and is currently evaluated in clinical trials for type 1 diabetes, cystic fibrosis and graft versus host disease. Thus, AAT therapy appears to have advanced from replacement therapy, to a safe and potential treatment for a broad spectrum of inflammatory and immune-mediated diseases.

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C-36 peptide, a degradation product of α1-antitrypsin, modulates human monocyte activation through LPS signaling pathways

Cited by 37 publications

References 47 publications

HDL functionality

HDL functionality

NF-κB Signaling, Elastase Localization, and Phagocytosis Differ in HIV-1 Permissive and Nonpermissive U937 Clones

Expanding the Clinical Indications for α1-Antitrypsin Therapy

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