Working from within: how secretory leukocyte protease inhibitor regulates the expression of pro-inflammatory genes

Douglas, Tinsley Claire; Hannila, Sari S.

doi:10.1139/bcb-2021-0284

Cited by 8 publications

(13 citation statements)

References 66 publications

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“…During systemic inflammation caused by trauma, infection, and autoinflammatory or autoimmune diseases, circulating pro-inflammatory mediators trigger acute-phase responses including the synthesis and release of the acute-phase reactants C-reactive protein (CRP), α1-antitrypsin (AAT), and secretory leukocyte protease inhibitor (SLPI) ( Gabay and Kushner, 1999 ; Douglas and Hannila, 2022 ). These acute-phase proteins exert pleiotropic functions including the facilitation of pathogen clearance, protection of the host from the attack of proteases mainly released from activated neutrophil granulocytes, and the modulation of inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…Much like AAT, SLPI inhibits serine proteases including neutrophil elastase, cathepsin G, and trypsin and protects pulmonary elastic fibers from degradation ( Williams et al, 2006 ). Independent of its anti-protease function, SLPI has protective anti-microbial, anti-inflammatory, and tolerogenic properties, while pro-inflammatory functions have not been described ( Nugteren and Samsom, 2021 ; Douglas and Hannila, 2022 ). SLPI is involved in wound healing, it regulates the formation of neutrophil extracellular traps, inhibits apoptosis, and regulates cell proliferation ( Nugteren and Samsom, 2021 ; Douglas and Hannila, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…Independent of its anti-protease function, SLPI has protective anti-microbial, anti-inflammatory, and tolerogenic properties, while pro-inflammatory functions have not been described ( Nugteren and Samsom, 2021 ; Douglas and Hannila, 2022 ). SLPI is involved in wound healing, it regulates the formation of neutrophil extracellular traps, inhibits apoptosis, and regulates cell proliferation ( Nugteren and Samsom, 2021 ; Douglas and Hannila, 2022 ). Accordingly, SLPI exerts modulatory and protective functions in numerous human and experimental diseases, including endotoxemia, infection, psoriasis, asthma, neuro-degeneration, obesity, diabetes type 2, and cancer ( Taggart et al, 2002 ; Taggart et al, 2005 ; Douglas and Hannila, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…SLPI is involved in wound healing, it regulates the formation of neutrophil extracellular traps, inhibits apoptosis, and regulates cell proliferation ( Nugteren and Samsom, 2021 ; Douglas and Hannila, 2022 ). Accordingly, SLPI exerts modulatory and protective functions in numerous human and experimental diseases, including endotoxemia, infection, psoriasis, asthma, neuro-degeneration, obesity, diabetes type 2, and cancer ( Taggart et al, 2002 ; Taggart et al, 2005 ; Douglas and Hannila, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…It physically interacts with CD14, which is together with TLR4 an essential part of the LPS receptor complex, and thereby interferes with LPS sensing ( Ding et al, 1999 ). Like AAT, SLPI is rapidly taken up by monocytes, where it can inhibit the proteolytic degradation of the inhibitor of κB and, hence, prevent the activation of NF-κB and the synthesis of pro-inflammatory cytokines ( Taggart et al, 2002 ; Taggart et al, 2005 ; Douglas and Hannila, 2022 ). In addition, SLPI can localize to cell nuclei and repress the function of pro-inflammatory genes by competing for NF-κB p 65 binding sites ( Taggart et al, 2005 ; Douglas and Hannila, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Negative regulation of ATP-induced inflammasome activation and cytokine secretion by acute-phase proteins: A mini review

2022

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The expression of the acute-phase reactants C-reactive protein (CRP), α1-antitrypsin (AAT), and secretory leukocyte protease inhibitor (SLPI), is induced in response to inflammation by pro-inflammatory mediators, including interleukin-1β. It is conceivable that acute-phase proteins exert protective functions, when the integrity of an organism is challenged by pathogens or trauma, which result in uncontrolled release of endogenous damage-associated molecular patterns like Toll-like receptor agonists and ATP. Acute-phase proteins can enhance or down-modulate immunity against infections or protect the host against damage caused by over-shooting effector functions of the immune system. CRP is mainly regarded as a pro-inflammatory opsonizing agent that binds to bacteria and damaged host cells thereby contributing to their inactivation and elimination. AAT and SLPI are well known for their anti-protease activity, which protects the lung extracellular matrix against degradation by proteases that are released by activated neutrophil granulocytes. In addition, there is growing evidence, that CRP, AAT, and SLPI can control the biosynthesis, maturation, and secretion of pro-inflammatory cytokines. The purpose of this narrative mini review is to summarize these anti-inflammatory functions with a focus on the negative control of the ATP-induced, inflammasome-dependent secretion of interleukin-1β by monocytes. CRP-, AAT- and SLPI-mediated control of interleukin-1β release involves the activation of unconventional nicotinic acetylcholine receptors that inhibits the ionotropic function of the ATP receptor P2X7. Apart from other functions, CRP, AAT, and SLPI seem to be central elements of systemic negative feedback loops that protect the host against systemic hyperinflammation, barrier dysfunction, and death by multiple organ damage.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Negative regulation of ATP-induced inflammasome activation and cytokine secretion by acute-phase proteins: A mini review

2022

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Dietary iron modulates gut microbiota and induces SLPI secretion to promote colorectal tumorigenesis

et al. 2023

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Dietary iron intake is closely related to the incidence of colorectal cancer. However, the interactions among dietary iron, gut microbiota, and epithelial cells in promoting tumorigenesis have rarely been discussed. Here, we report that gut microbiota plays a crucial role in promoting colorectal tumorigenesis in multiple mice models under excessive dietary iron intake. Gut microbiota modulated by excessive dietary iron are pathogenic, irritating the permeability of the gut barrier and causing leakage of lumen bacteria. Mechanistically, epithelial cells released more secretory leukocyte protease inhibitor (SLPI) to combat the leaked bacteria and limit inflammation. The upregulated SLPI acted as a pro-tumorigenic factor and promoted colorectal tumorigenesis by activating the MAPK signaling pathway. Moreover, excessive dietary iron significantly depleted Akkermansiaceae in the gut microbiota; while supplementation with Akkermansia muciniphila could successfully attenuate the tumorigenic effect from excessive dietary iron. Overall, excessive dietary iron perturbs diet – microbiome–epithelium interactions, which contributes to intestinal tumor initiation.

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State of local cervical immunity in women with infertility

Sereda

2023

UJHW

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Purpose - to study certain indicators of local immunity in women with infertility of various origins and early cervical lesions Materials and methods. The state of local cervical immunity was examined in 496 women, who were divided into groups depending on the cause of infertility, and each group was divided into subgroups A and B depending on the presence of cervical epithelial lesions. 128 women in the Group I had an endocrine cause, 122 patients in the Group II had a tubal-peritoneal factor of infertility, and 121 patients in the Group III had a male factor of fertility disorder. 125 healthy women formed the control group (CG). Subgroup A included women with NILM liquid cytology results: IA - 100 women, IIA - 70, IIIA - 68, GCA - 88. Subgroups B included women with ASC-US (atypical squamous cells of undetermined significance), LSIL (low-grade squamous intraepithelial lesion) and HSIL (high-grade squamous intraepithelial lesion): IB - 28 patients, IIB - 52, IIIB - 53, CGB - 37. In all patients, the content of interleukin-8 and -6 (IL-8, IL-6), lactoferrin and secretory leukocyte proteinase inhibitor in the material obtained for liquid cytology was determined by polymerase chain reaction. Results. In all patients with infertility, an increased concentration of secretory leukocyte proteinase inhibitor (from 314.1 to 398.7 pg/ml) and a decreased lactoferrin content (from 13.6 to 28.6 pg/ml) were found compared to the group of healthy women (114.8 and 64.8 pg/ml, respectively). In women with tubal and peritoneal infertility and male infertility, higher concentrations of IL-8 were found (659.9 to 878.8 pg/ml) than in the group of endocrine infertility (302.9 pg/ml) and in the group of healthy women (282.4 pg/ml). Conclusions. IL-8 content in cervical mucus is probably higher in women with tubal-peritoneal infertility (838 pg/ml) and male infertility (659.9 pg/ml) than in healthy women (289.4 pg/ml) and in women with endocrine infertility (302.3 pg/ml). The content of secretory inhibitor of leukocyte proteinase in cervical mucus was increased in all patients with infertility, regardless of its cause (from 314.1 pg/ml to 398.9 pg/ml), in the group of healthy women - 144.8 pg/ml. 3. The content of lactoferrin in the mucus of the cervical canal was reduced in all patients with impaired fertility (from 13.6 pg/ml to 28.6 pg/ml), in the group of healthy women - 64.8 pg/ml. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the author.

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Working from within: how secretory leukocyte protease inhibitor regulates the expression of pro-inflammatory genes

Cited by 8 publications

References 66 publications

Negative regulation of ATP-induced inflammasome activation and cytokine secretion by acute-phase proteins: A mini review

Negative regulation of ATP-induced inflammasome activation and cytokine secretion by acute-phase proteins: A mini review

Dietary iron modulates gut microbiota and induces SLPI secretion to promote colorectal tumorigenesis

State of local cervical immunity in women with infertility

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