An Emerging Role for Serine Protease Inhibitors in T Lymphocyte Immunity and Beyond

Ashton‐Rickardt, Philip G.

doi:10.5402/2012/354365

Cited by 7 publications

(6 citation statements)

References 145 publications

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“…Of note, the Sb1-mediated mechanism proposed here as the basis of the IL-1β and IL-23-driven TH cell encephalitogenic program, although new for CD4 cells, is not unique, but rather is analogous to the mechanisms by which Sb9 controls expansion and retraction of human and mouse populations of activated CD8 cytolytic cells and NK cells (22,46). In a similar program, Sb1 reacts stoichiometrically with endogenous granule serine proteases cathepsin G and proteinase-3 to control neutrophil survival (34,35).…”

Section: Discussionmentioning

confidence: 90%

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SerpinB1 controls encephalitogenic T helper cells in neuroinflammation

Hou

Rao

Yuki

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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SerpinB1, a protease inhibitor and neutrophil survival factor, was recently linked with IL-17–expressing T cells. Here, we show that serpinB1 (Sb1) is dramatically induced in a subset of effector CD4 cells in experimental autoimmune encephalomyelitis (EAE). Despite normal T cell priming, Sb1−/− mice are resistant to EAE with a paucity of T helper (TH) cells that produce two or more of the cytokines, IFNγ, GM-CSF, and IL-17. These multiple cytokine-producing CD4 cells proliferate extremely rapidly; highly express the cytolytic granule proteins perforin-A, granzyme C (GzmC), and GzmA and surface receptors IL-23R, IL-7Rα, and IL-1R1; and can be identified by the surface marker CXCR6. In Sb1−/− mice, CXCR6+ TH cells are generated but fail to expand due to enhanced granule protease-mediated mitochondrial damage leading to suicidal cell death. Finally, anti-CXCR6 antibody treatment, like Sb1 deletion, dramatically reverts EAE, strongly indicating that the CXCR6+ T cells are the drivers of encephalitis.

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Section: Discussionmentioning

confidence: 90%

“…We then considered whether the Sb1-dependent CD4 cells are subject to self-inflicted cell death as occurs in other granulecontaining cells such as NK cells, CD8 cells, and neutrophils (22,34,35,46). In this mechanism, high-level activation or stress causes permeabilization of granule membranes allowing granzymes to leak into the cytoplasm (47).…”

Section: Resultsmentioning

confidence: 99%

SerpinB1 controls encephalitogenic T helper cells in neuroinflammation

Hou

Rao

Yuki

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…However, lately some of them (e.g. BBI) have been found beneficial to humans and animals by exerting bioactive, therapeutic, or immune‐therapeutic effects (Ashton‐Rickardt, 1998; Awosika and Aluko, 2019; Kennedy, 1998). With an increasing use of plant proteins for food and feed, accurate measurement of trypsin inhibitor activity (TIA) becomes more important than ever.…”

Section: Introductionmentioning

confidence: 99%

Trypsin Inhibitor Assay: Expressing, Calculating, and Standardizing Inhibitor Activity in Absolute Amounts of Trypsin Inhibited or Trypsin Inhibitors

Liu

2021

J Americ Oil Chem Soc

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For expressing trypsin inhibitor activity (TIA), trypsin units inhibited (TUI), trypsin inhibited, and trypsin inhibitors have been used. Although the last two units are preferred, their calculations in current practices require refinement. With the proposed AOCS method Ba 12a-2020, four experiments were conducted, using four trypsin preparations having specific activity of 11,625, 12,602, 13,728, and 14,926 Nα-benzoyl-L-arginine ethyl ester (BAEE) units/mg protein, respectively. Experiment 1 determined the relationship between absorbance at 410 nm (A410) and trypsin concentration. Experiment 2 involved assaying raw and heated soybeans, expressing TIA as TUI/ mg sample and μg trypsin inhibited/mg sample, and determining conversion factors between the two units. Experiment 3 resembled Experiment 2 except for using purified soybean Kunitz inhibitor (KTI) and Bowman-Birk inhibitor (BBI). Conversion factors determined correlated highly with trypsin-specific activity (R 2 = 0.9789). After standardizing against a reference trypsin having 15,000 BAEE units/mg protein, a standardized conversion factor of 0.03 A410 (1.5 TUI) = 1 μg trypsin inhibited was determined. It remained consistent regardless of trypsin specific activity, with or without inhibitors, and type of inhibitor samples. By using purified inhibitors (Experiment 3), conversion values between TUI and μg trypsin inhibitor and between μg trypsin inhibited and μg trypsin inhibitor could also be calculated, enabling expression of TIA in amounts of pure KTI, BBI or their equivalents. Furthermore, when the AOCS method was modified with half substrate concentration, half trypsin concentration or half both (Experiment 4), TIA values in TUI could change with modifications but values in mg trypsin inhibited (standardized) or trypsin inhibitor remained consistent.

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“…Therefore, for many years, TI has been considered a key antinutritional factor (Gatel, 1994). Yet, in recent years, some serpins (such as soybean Bowman‐Birk inhibitor) have been found to be beneficial to humans and animals by being bioactive, therapeutic, or immunotherapeutic (Ashton‐Rickardt, 2012; Awosika and Aluko, 2019; Kennedy, 1998). They can also be used as food‐processing agents to control the extent of unwanted proteolytic degradation in animal muscles and cereal flours (Singh and Benjakul, 2018) or serve as predictors of meat tenderness (Boudida et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

An International Collaborative Study on Trypsin Inhibitor Assay for Legumes, Cereals, and Related Products

Liu

Seegers

Cao³

et al. 2021

J Americ Oil Chem Soc

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For determining trypsin inhibitor activity (TIA) in soy products, the American Oil Chemists' Society (AOCS) Method Ba 12-75 has been used. It measures differences in absorbance at 410 nm of bovine trypsin activity toward a synthetic substrate (Nα-benzoyl-DL-arginine-p-nitroanilide) in the absence and presence of an inhibitor. Recently, a significantly improved method was developed (JAOCS, 2019, 96:635-645), featuring 5 mL of total assay volume, enzymelast sequence, and single inhibitor level in duplicate. It is proposed as the AOCS Method Ba 12a-2020. As a part of the AOCS method approval process, a collaborative study involving 12 international laboratories was conducted to evaluate the performance of the proposed method. The study involved measuring TIA in 10 selected test samples plus a blind duplicate. They included soybeans, pulses, cereals, and their processed products (flours, concentrates, and isolates). After rigorous statistical treatment of the data, only three outliers were removed from the data of two samples. Repeatability relative standard deviations (RSDr) for the 11 samples ranged from 0.99% to 5.52%. Reproducibility RSD (RSD R ) ranged from 7.07% to 22.92%, with seven samples having RSD R around 10% or less. The remaining four samples had very low TIA, and their RSD R values ranged from 13.34% to 22.92%. The study has demonstrated reliable performance of the proposed AOCS method. Several collaborators carried out additional experiments addressing some aspects of the method, leading to further refinements. The proposed method is undergoing evaluation by the AOCS Uniform Methods Committee for adoption as an Official Method for measuring TIA in various legume and grain products.

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An Emerging Role for Serine Protease Inhibitors in T Lymphocyte Immunity and Beyond

Cited by 7 publications

References 145 publications

SerpinB1 controls encephalitogenic T helper cells in neuroinflammation

SerpinB1 controls encephalitogenic T helper cells in neuroinflammation

Trypsin Inhibitor Assay: Expressing, Calculating, and Standardizing Inhibitor Activity in Absolute Amounts of Trypsin Inhibited or Trypsin Inhibitors

An International Collaborative Study on Trypsin Inhibitor Assay for Legumes, Cereals, and Related Products

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