Neurotensin-based hybrid peptide's anti-inflammatory activity in murine model of a contact sensitivity response

Kaczyńska, Katarzyna; Kogut, Ewelina; Zając, Dominika; Jampolska, Monika; Andrzejewski, Kryspin; Sulejczak, Dorota; Lipkowski, Andrzej W.; Kleczkowska, Patrycja

doi:10.1016/j.ejps.2016.08.012

Cited by 9 publications

(8 citation statements)

References 28 publications

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“…One of the hybrid peptides, designated PK20, comprises modified endomorphin-2 (EM-2) and neurotensin (NT) pharmacophores, and it has been shown previously as a highly potent analgesic, as well as a neuroprotective agent [13,14]. Detailed information on the hybrid structure, amino acid modification, and an improved stability can be found elsewhere [13,15]. Both elements of the ligand seem to possess anti-inflammatory potency.…”

Section: Introductionmentioning

confidence: 99%

Endomorphin-2- and Neurotensin- Based Chimeric Peptide Attenuates Airway Inflammation in Mouse Model of Nonallergic Asthma

Russjan

Andrzejewski

Sulejczak

et al. 2019

IJMS

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We examined anti-inflammatory potency of hybrid peptide-PK20, composed of neurotensin (NT) and endomorphin-2 (EM-2) pharmacophores in a murine model of non-atopic asthma induced by skin sensitization with 2,4-dinitrofluorobenzene and intratracheal challenge of cognate hapten. Mice received intraperitoneally PK20, equimolar mixture of its structural elements (MIX), dexamethasone (DEX), or NaCl. Twenty-four hours following hapten challenge, the measurements of airway responsiveness to methacholine were taken. Bronchoalveolar lavage (BALF) and lungs were collected for further analyses. Treatment with PK20, similarly to dexamethasone, reduced infiltration of inflammatory cells, concentration of mouse mast cell protease, IL-1β, IL-12p40, IL-17A, CXCL1, RANTES in lungs and IL-1α, IL-2, IL-13, and TNF-α in BALF. Simple mixture of NT and EM-2 moieties was less potent. PK20, DEX, and MIX significantly decreased malondialdehyde level and secretory phospholipase 2 activity in lungs. Intensity of NF-κB immunoreactivity was diminished only after PK20 and DEX treatments. Neither PK20 nor mixture of its pharmacophores were as effective as DEX in alleviating airway hyperresponsiveness. PK20 effectively inhibited hapten-induced inflammation and mediator and signaling pathways in a manner seen with dexamethasone. Improved anti-inflammatory potency of the hybrid over the mixture of its moieties shows its preponderance and might pose a promising tool in modulating inflammation in asthma.

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Section: Introductionmentioning

confidence: 99%

Endomorphin-2- and Neurotensin- Based Chimeric Peptide Attenuates Airway Inflammation in Mouse Model of Nonallergic Asthma

Russjan

Andrzejewski

Sulejczak

et al. 2019

IJMS

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“…Primary skin infections stimulate inflammatory response which plays an essential role in the defense against pathogens [ 22 ]. This response involves a complex interplay of cytokines and chemokines, such as the pro-inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) [ 23 ]. Therefore, we used the ELISA method to detect the changes of IL-6, TNF-α, and VEGF after drug treatment.…”

Section: Resultsmentioning

confidence: 99%

In Vitro and In Vivo Activity of 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] Mutilin against Methicillin-Resistant Staphylococcus aureus

Leng

Fan

et al. 2021

Molecules

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Staphylococcus aureus (S. aureus) is a major human pathogen that requires new antibiotics with unique mechanism. A new pleuromutilin derivative, 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] mutilin (DPTM), has been synthesized and proved as a potent antibacterial agent using in vitro and in vivo assays. In the present study, DPTM was further in vitro evaluated against methicillin-resistant Staphylococcus aureus (MRSA) isolated from dairy farms and outperformed tiamulin fumarate, a pleuromutilin drug used for veterinary. Moreover, a murine skin wound model caused by MRSA infection was established, and the healing effect of DPTM was investigated. The results showed that DPTM could promote the healing of MRSA skin infection, reduce the bacterial burden of infected skin MRSA and decrease the secretion of IL-6 and TNF-α inflammatory cytokines in plasma. These results provided the basis for further in-depth drug targeted studies of DPTM as a novel antibacterial agent.

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“…Эндоморфины могут регулировать выраженность реакции гиперчувствительности. Установлено, что гибридный пептид PK20, включающий в свой состав аналог ЭМ-2 и модифицированный фрагмент нейротензина (8-13), снижает интенсивность кожной реакции на динитрофторбензол и угнетает локальную продукцию IL-1α, MCP-1, TNF-α [41]. В литературе есть данные об антипролиферативном эффекте эндоморфинов, поскольку они способны регулировать интенсивность пролиферации через усиление апоптотических процессов.…”

Section: адаптивный иммунитетunclassified

Endomorphins: structure, localization, immunoregulatory activity

Гейн¹,

Baeva²

2020

Probl Endokrinol (Mosk)

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Endomorphins endogenous tetrapeptides with the highest affinity for the -opioid receptor. Distribution of endomorphins in the immune system, similar to that of other opioid peptides, has allowed to suggest their active participation in the processes of immune regulation. This review summarizes modern views on the structure of endomorphins, their localization, possible intracellular mechanisms of signal transmission and their effects on the processes of activation, proliferation and differentiation of cells of innate and adaptive immunity. Endomorphins actively modulate functions of the cells of the immune system, while peptides predominantly suppress adaptive immunity reactions, but the effects on innate immunity can be either depressing or stimulating. Thus, endomorphins can be promising compounds that can effectively regulate both nociceptive signals and processes in the immune system.

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Neurotensin-based hybrid peptide's anti-inflammatory activity in murine model of a contact sensitivity response

Cited by 9 publications

References 28 publications

Endomorphin-2- and Neurotensin- Based Chimeric Peptide Attenuates Airway Inflammation in Mouse Model of Nonallergic Asthma

Endomorphin-2- and Neurotensin- Based Chimeric Peptide Attenuates Airway Inflammation in Mouse Model of Nonallergic Asthma

In Vitro and In Vivo Activity of 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] Mutilin against Methicillin-Resistant Staphylococcus aureus

Endomorphins: structure, localization, immunoregulatory activity

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