Collagenases in an ether extract of bacterial metabolites used as an immunostimulator induces TNF-α and IFN-γ

Singh, Namrata; Bhattacharyya, Debasish

doi:10.1016/j.intimp.2014.08.026

Cited by 15 publications

(13 citation statements)

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“…The nonspecific immune stimulatory drug used in this study was manufactured and supplied by M/s Union Drugs Co. Ltd., Kolkata, India under the trade name “Sterodin.” It is constituted of an ether extract of nine bacterial metabolites in combination with solvent extracts of ox bile lipids. Composition of the final aqueous solution has been described earlier (Singh and Bhattacharyya, , , ).…”

Section: Methodsmentioning

confidence: 99%

“…Cells were harvested after growing to confluence. Cell viability was estimated by trypan blue dye exclusion test (Singh and Bhattacharyya, ).…”

Section: Methodsmentioning

confidence: 99%

“…Cell viability was estimated by the addition of 10 μl of 5 mg/ml of MTT to each well. After incubation for 4 h at 37°C, rest of the experiment was followed as described in Singh and Bhattacharyya ().…”

Section: Methodsmentioning

confidence: 99%

“…Samples as described previously were added to the wells and incubated at 37°C. Rest of the protocol was followed as described in Singh and Bhattacharyya ().…”

Section: Methodsmentioning

confidence: 99%

“…It is our current interest to evaluate a nonspecific immunostimulatory drug (described later) that is composed of extracts from bacterial metabolites and bile lipid in terms of their active ingredients and mechanisms of action (Ray et al, ; Singh and Bhattacharyya, ). This drug can stabilize Proteinase K. Considering natural degradation of proteases by auto‐digestion in particular for those having broad specificity, reversible inactivation of Proteinase K is obligatory to maintain its activity (De et al, ; Sharma et al, ).…”

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confidence: 99%

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Cholesterol and Its Derivatives Reversibly Inhibit Proteinase K

Singh

Bhattacharyya

2016

J. Cell. Physiol.

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Microorganisms express a variety of proteases that degrade many proteins of the host body and subvert host immune response. While elucidating the mechanism/s of an immune stimulatory drug that contains bile lipid, regulation of proteolytic activity was investigated. The drug and bile lipids both stabilize Proteinase K, an aggressive protease of fungal origin against auto-digestion. Among the components of bile lipids, only cholesterol and its derivatives stabilize the enzyme. Biophysical evidences such as scattering of light, intrinsic and extrinsic fluorescence emission spectra, circular dichroism spectra, atomic force microscopy, and transmission electron microscopy images indicated that cholesterol and its derivatives interact with Proteinase K. Inhibition kinetics using esterolysis of ATEE revealed non-competitive inhibition by cholesterol. Surface Plasmon Resonance and mass spectrometric analysis indicated 1:1 stoichiometry of binding and with dissociation constant in the μM range. Further, the presence of four cholesterol recognition amino acid consensus motifs (CRAC motifs I-IV) was identified in Proteinase K. Bioinformatics analysis revealed that the whole stretch of cholesterol interacts very well with the hydrophobic groove of motif II only among the four CRAC motifs. Variation of cholesterol content of HepG2 human liver carcinoma cells showed positive correlation with binding of fluorescence tagged Proteinase K. Under these conditions, binding of Proteinase K to the cells did not affect their morphology, viability and growth kinetics. Cell bound Proteinase K could be released by an excess of its substrate, thereby restoring reversibly its proteolytic activity. J. Cell. Physiol. 232: 596-609, 2017. © 2016 Wiley Periodicals, Inc.

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Section: Methodsmentioning

confidence: 99%

“…Cells were harvested after growing to confluence. Cell viability was estimated by trypan blue dye exclusion test (Singh and Bhattacharyya, ).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Samples as described previously were added to the wells and incubated at 37°C. Rest of the protocol was followed as described in Singh and Bhattacharyya ().…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Cholesterol and Its Derivatives Reversibly Inhibit Proteinase K

Singh

Bhattacharyya

2016

J. Cell. Physiol.

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Therapeutic applications and biological activities of bacterial bioactive extracts

et al. 2021

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Bacteria are rich in a wide variety of secondary metabolites, such as pigments, alkaloids, antibiotics, and others. These bioactive microbial products serve a great application in human and animal health. Their molecular diversity allows these natural products to possess several therapeutic attributes and biological functions. That’s why the current natural drug industry focuses on uncovering all the possible ailments and diseases that could be combated by bacterial extracts and their secondary metabolites. In this paper, we review the major utilizations of bacterial natural products for the treatment of cancer, inflammatory diseases, allergies, autoimmune diseases, infections and other diseases that threaten public health. We also elaborate on the identified biological activities of bacterial secondary metabolites including antibacterial, antifungal, antiviral and antioxidant activities all of which are essential nowadays with the emergence of drug-resistant microbial pathogens. Throughout this review, we discuss the possible mechanisms of actions in which bacterial-derived biologically active molecular entities could possess healing properties to inspire the development of new therapeutic agents in academia and industry.

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The potential of immunomodulators in shaping the future of healthcare

Sharma,

Arora,

Bala

2024

Discov Med

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Immunomodulators play a crucial role in modern medical practice, offering both stimulatory and suppressive effects to regulate and control the immune response. These substances, which include immunostimulants and immunosuppressants, modulate the immune system by delivering cytokines and stimulating immune cells. Immunosuppressants are vital in liver and kidney transplantation, where they reduce the immune system’s activation to prevent organ rejection. They are also essential in managing autoimmune disorders by providing controlled suppression of immune activities to avoid self-damage. Conversely, immunostimulants enhance the body’s innate immunity, preventing infections, and boosting resistance against various viral and bacterial diseases. These agents strengthen the body’s natural defenses, making them indispensable in infection control and immunoprophylaxis. The mechanisms of immunomodulators are intricate, involving interactions with key molecules such as cytokines and signaling pathways to shape immune responses, mitigate inflammation, and regulate immune cell functions. Mesenchymal stem cells (MSCs) have emerged as a promising component due to their ability to suppress immune reactions, regulate inflammatory responses, induce immune tolerance, and aid in tissue regeneration. MSCs’ unique properties underscore their potential in treating immune-related disorders, supporting organ transplantation, and promoting tissue repair. Clinically, immunomodulators are central to managing autoimmune diseases, enhancing cancer immunotherapy, combating infectious diseases, and preventing organ rejection in transplant recipients. Innovative therapies like checkpoint inhibitors, CAR T-cell therapy, and cancer vaccines have revolutionized oncology by leveraging the immune system's capabilities. This review explores the critical roles and mechanisms of immunomodulators, highlighting their impact on contemporary healthcare and their potential for future therapeutic developments.Graphical Abstract

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Collagenases in an ether extract of bacterial metabolites used as an immunostimulator induces TNF-α and IFN-γ

Cited by 15 publications

References 48 publications

Cholesterol and Its Derivatives Reversibly Inhibit Proteinase K

Cholesterol and Its Derivatives Reversibly Inhibit Proteinase K

Therapeutic applications and biological activities of bacterial bioactive extracts

The potential of immunomodulators in shaping the future of healthcare

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