Link between mast cells and bacteria: Antimicrobial defense, function and regulation by cytokines

Conti, Pio; Caraffa, Alessandro; Ronconi, Gianpaolo; Lessiani, Gianfranco; Theoharides, Theoharis C.

doi:10.1016/j.mehy.2017.06.018

Cited by 20 publications

(12 citation statements)

References 56 publications

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“…Bacteria and their products, such as LPS, are pronociceptive substances which, via TLR4, induce MCs to release cytokines such as TNF, IL‐6, and proinflammatory IL‐1 family members, which participate in immune responses during pathogen infection (Conti et al, ; Conti et al, ; Conti et al, ; Conti, Ronconi, Caraffa, Lessiani, & Duraisamy, ). The IL‐1 family of cytokines is composed of 11 isoforms, all of which induce inflammation.…”

Section: Il‐1mentioning

confidence: 99%

“…IL‐37 acts through an intracellular mechanism translocating to the nucleus, and it downregulates the expression of cJun, mitogen‐activated protein kinases (MAP) kinase p38α, signal transducer and activator of transcription (STAT) transcription factors, and p53, which are involved as proinflammatory signals (Cavalli et al, ; Conti, Carinci, Caraffa, et al, ; Conti, Carinci, Lessiani, et al, ; Conti, Lessiani, Kritas, et al, ; Conti, Ronconi, Caraffa, et al, ).…”

Section: Il‐37mentioning

confidence: 99%

“…Inhibitors of this cytokine family, such as IL‐1 receptor antagonist (IL‐1RA) or IL‐37, can provide pain relief and provoke an improvement in neuropathy and stress‐induced skin disorders. IL‐37 exhibits an important inhibition of the pain and inflammation induced by proinflammatory IL‐1 family on MCs, with a great improvement in the severity of FM symptoms (Conti, Carinci, Caraffa, et al, ; Conti, Carinci, Lessiani, et al, ; Conti, Lessiani, Kritas, et al, ; Conti, Ronconi, Caraffa, et al, ).…”

Section: Il‐37mentioning

confidence: 99%

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Impact of mast cells in fibromyalgia and low‐grade chronic inflammation: Can IL‐37 play a role?

Conti

Gallenga

Caraffa

et al. 2019

Dermatologic Therapy

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Fibromyalgia (FM) is a disease characterized by chronic widespread pain, fatigue, aches, joint stiffness, depression, cognitive dysfunction, and nonrestorative sleep. In FM, neurotransmission and glial activation can occur with an increase in inflammatory cytokines and involvement of mast cells (MCs) in the skin. FM skin biopsiesshow an increase in the number of MCs, as well as the production of corticotropin releasing hormone and substance P (SP) by the neurons, which in turn activate MCs to release neurosensitizing proinflammatory substances, such as cytokines, secreted preformed mediators, and lipids, which can exacerbate low-grade inflammation. In fact, certain proinflammatory cytokines are higher in FM and mediate muscle pain, the mechanism of which is not yet clear. MC-derived tumor necrosis factor (TNF) induces nerve growth factor (NGF) and participates in nerve fiber elongation in skin hypersensitivity. IL-37 is an inhibitor of proinflammatory IL-1 family members, which are generated and released by MCs. The goal of this article is to demonstrate that inflammatory cytokines and MC products play a role in FM and that inflammation may be inhibited by IL-37. Here, we propose IL-37 as a cytokine that contributes to improve the pathogenesis of FM by blocking IL-1 family members.

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Section: Il‐1mentioning

confidence: 99%

Section: Il‐37mentioning

confidence: 99%

Section: Il‐37mentioning

confidence: 99%

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Impact of mast cells in fibromyalgia and low‐grade chronic inflammation: Can IL‐37 play a role?

Conti

Gallenga

Caraffa

et al. 2019

Dermatologic Therapy

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“…In addition to being produced by MCs, LL-37 is also a MC activator[20,21]. LL37 induces MC migration[21], which may complement the antimicrobial properties of MCs since LL-37 may attract MCs towards infection sites to allow inflammatory mediators produced by MCs, such as Interleukin (IL)-1 and −8 and TNF and host defense peptides, contribute to host defense against bacteria and viruses[22]. Similarly, other peptides that activate MCs to degranulate, including retrocyclins (RC101) and protegrin-1, have antimicrobial properties and can kill E.coli in a dose-dependent manner[23].…”

Section: Mast Cell Activators As Antimicrobialsmentioning

confidence: 99%

Mast cell activators as novel immune regulators

Johnson‐Weaver

Choi

Abraham

et al. 2018

Current Opinion in Pharmacology

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Mast cells are an important cell type of the innate immune system that when activated, play a crucial role in generating protective innate host responses after bacterial and viral infection. Additionally, activated mast cells influence lymph node composition to regulate the induction of adaptive immune responses. The recognition that mast cells play a beneficial role in host responses to microbial infection and induction of adaptive immunity has provided the rationale to evaluate mast cell activators for use as antimicrobials or vaccine adjuvants. This review summarizes the role of mast cell activators in antimicrobial responses while also discussing the use of different classes of mast cell activators as potent vaccine adjuvants that enhance the induction of protective immune responses.

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“…Hence, MCs participate in maintaining body homeostasis and various physiological and pathological processes including allergic reactions and are well known for their involvement in host defense. [21][22][23][24][25] Importantly, MCs are widely recognized as primary effector cells of inflammatory processes, as they affect different stages of inflammation, including its initiation and maintenance, as well as its resolution. Hence, they are involved in both acute and chronic as well as low-grade inflammation.…”

Section: Introductionmentioning

confidence: 99%

Adipocytokines leptin and adiponectin function as mast cell activity modulators

et al. 2019

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Summary A growing body of data indicates that adipocytokines, including leptin and adiponectin, are critical components not only of metabolic regulation but also of the immune system, mainly by influencing the activity of cells participating in immunological and inflammatory processes. As mast cells (MCs) are the key players in the course of those mechanisms, this study aimed to evaluate the impact of leptin and adiponectin on some aspects of MC activity. We documented that in vivo differentiated mature tissue MCs from the rat peritoneal cavity express a receptor for leptin (OB‐R), as well as receptors for adiponectin (AdipoR1 and AdipoR2). We established that leptin, but not adiponectin, stimulates MCs to release of histamine as well as to generation of cysteinyl leukotrienes (cysLTs) and chemokine CCL2. We also found that both adipocytokines affect mRNA expression of various cytokines/chemokines. Leptin and adiponectin also activate MCs to produce reactive oxygen species. Moreover, we documented that leptin significantly augments the surface expression of receptors for cysLTs, i.e. CYSLTR1, CYSLTR2, and GPR17 on MCs, while adiponectin increases only GPR17 expression, and decreases CYSLTR2. Finally, we showed that both adipocytokines serve as potent chemoattractants for MCs. In intracellular signaling in MCs activated by leptin Janus‐activated kinase 2, phospholipase C, phosphatidylinositol 3‐kinase (PI3K), extracellular signal‐regulated kinase (ERK1/2), and p38 molecules play a part whereas the adiponectin‐induced activity of MCs is mediated through PI3K, p38, and ERK1/2 pathways. Our observations that leptin and adiponectin regulate MC activity might indicate that adipocytokines modulate the different processes in which MCs are involved.

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Link between mast cells and bacteria: Antimicrobial defense, function and regulation by cytokines

Cited by 20 publications

References 56 publications

Impact of mast cells in fibromyalgia and low‐grade chronic inflammation: Can IL‐37 play a role?

Impact of mast cells in fibromyalgia and low‐grade chronic inflammation: Can IL‐37 play a role?

Mast cell activators as novel immune regulators

Adipocytokines leptin and adiponectin function as mast cell activity modulators

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