Inflammation signaling

Inflammation is a coordinated tissue response to injury, pathogens, or metabolic stress, engaging PRRs, NF-κB/IRF, MAPK, inflammasomes, and JAK–STAT hubs to produce cytokines, chemokines, and lipid mediators. Chronic or dysregulated inflammation links to hyperalgesia, metabolic disease, neurodegeneration, and IBD; TRP ion channels on sensory neurons are key effectors downstream of many inflammatory mediators.

1. Key targets

Core nodes

  • PRR 与炎症小体

    TLRs, NLRs, cGAS–STING sense PAMPs/DAMPs; NLRP3-class inflammasomes activate caspase-1 for IL-1β/IL-18 maturation.

  • NF-κB / MAPK / JAK–STAT

    Rapid induction of TNF, IL-6, type I IFNs; JAK–STAT sustains programs and leukocyte fate decisions.

  • Lipid mediators & enzymes

    COX/LOX produce prostanoids and leukotrienes—vascular permeability, fever, and pain modulation.

Innate–adaptive interface

  • DCs/macrophages present antigen and secrete IL-12/IL-23
  • Th1/Th17/Treg balance shapes tissue injury vs resolution

Resolution & models

  • Pro-resolving mediators and macrophage polarization promote resolution
  • Human vs murine immune composition differs—extrapolate carefully

2. Suggested experimental readouts

Separate systemic vs local readouts and acute vs chronic phases; pair phospho with total protein and rigorous stimulation controls.

  • p65 nuclear translocation or phospho-IκB; NLRP3/ASC specks (IF)
  • Secreted IL-1β, IL-6, TNF, IFNs (ELISA / intracellular FC / scRNA-seq)
  • Cleaved caspase-1 and mature IL-1β (inflammasome activity)
  • iNOS/COX-2, chemokines, adhesion molecules (tissue inflammation panel)
  • Ca² imaging or patch clamp for TRP function (specialized platforms)

3. Major hubs (summary)

PathwayTypical triggersRepresentative readouts
NF-κBTLR、TNF-R、IL-1R、抗原受体协同p65 入核、IκB 降解、炎症基因转录
NLRP3 炎症小体Crystals, ATP, lysosomal damage, K⁺ effluxASC 寡聚、IL-1β 成熟、LDH 释放（模型依赖）
JAK–STATI/II 型细胞因子STAT1/3/6 磷酸化、SOCS 反馈

4. Therapeutic & translational context

  • NSAIDs / COX 抑制: reduce prostanoid synthesis; GI and cardiovascular risk with chronic use.
  • 糖皮质激素: broad anti-inflammatory; genomic and non-genomic effects—dose/time controls.
  • 生物制剂与小分子: anti-TNF, anti-IL-6R, IL-1 blockade, JAK inhibitors reshaped autoimmunity and IBD care.

Inflammation-related antibodies (curated)

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5. Product lines & on-site search

Primary & phospho antibodies

IL-1β, IL-6, TNF-α, IFN-γ, NLRP3, ASC, caspase-1, NF-κB/p65, p-STAT, COX-2, iNOS, TRPV1/TRPA1, tight junction proteins, FoxP3—WB/IHC/IF/FC per clone/species.

6. Inhibitors & tool compounds (summary)

For research use; follow lab SOP, compound datasheets, and ethics approvals.

MCC950

NLRP3 inhibitor (research tool).

Bay 11-7082

IκB phosphorylation blocker–class tool (cytotoxicity caution).

Ruxolitinib / Tofacitinib

JAK inhibitor prototypes for cytokine-axis studies.

Parthenolide

Natural-product NF-κB probe (among others).

Z-VAD-FMK

Pan-caspase inhibitor; common inflammasome control.

Capsazepine

TRPV1 antagonist (classic pharmacology tool).

7. Pathway schematic

PRR–cytokines–mediators–TRP / mucosa schematic
Inflammation pathway schematic
Legend
  1. PRRs and inflammasomes drive acute mediators
  2. Cytokine networks amplify and recruit leukocytes
  3. Prostanoids/bradykinin modulate TRP channel activity
  4. Mucosal immunity and genetics shape chronic IBD phenotypes

8. Pathway biology overview

Acute inflammation aims to clear pathogens and initiate repair; chronic inflammation couples to remodeling, fibrosis, and tumor microenvironment reprogramming. The same mediator can have opposing effects by cell type and niche—annotate source, species, and disease stage.

  • Cytokine storm reflects runaway positive feedback—distinct from local inflammation
  • Microbiota and metabolites (e.g., SCFAs) tune mucosal immune homeostasis

Inflammatory mediator regulation of TRP channels

Transient receptor potential (TRP) channels (e.g., TRPV1, TRPA1, TRPM8) are expressed on sensory neurons and some immune cells. They are gated or modulated by temperature, osmotic stress, redox cues, and numerous inflammatory mediators, contributing to hyperalgesia, neurogenic inflammation, and reflex vasomotor responses.

  • Prostaglandin E₂ can sensitize TRPV1 via GPCR–PKA/PKC signaling, lowering heat pain thresholds.
  • Bradykinin, lipoxygenase products, and ROS can activate or potentiate TRPA1-mediated chemonociception.
  • Histamine and serotonin can indirectly modulate TRP activity via coupled receptors, linking to itch and flush.

KEGG map: hsa04750 Inflammatory mediator regulation of TRP channels

Inflammatory bowel disease

Inflammatory bowel disease (IBD) chiefly comprises ulcerative colitis (UC) and Crohn disease (CD)—chronic relapsing intestinal inflammation driven by genetic susceptibility, epithelial barrier defects, dysbiosis, and dysregulated innate/adaptive immunity (e.g., IL-23–Th17 axis, TNF-driven neutrophil recruitment).

Ulcerative colitis (UC)

Continuous mucosal inflammation typically involving colon and rectum; hallmark bloody diarrhea; mucosa-predominant (deeper extension in advanced disease).

Crohn disease (CD)

Segmental transmural inflammation anywhere along the GI tract; fistulae, strictures, and extraintestinal manifestations are relatively common.

  • Genetics: NOD2, ATG16L1, IL23R variants associate with risk (population-dependent)
  • Trials often pair calprotectin, CRP, endoscopic scores, and histologic activity

KEGG map: hsa05321 Inflammatory bowel disease

9. Related pathways on this site

NF-κBTGF-β/SmadMAPK/ERKPI3K/Akt/mTORJAK-STATApoptosisAutophagyER stressUnfolded protein response

10. External databases & modification resources

11. References

Inflammation & cytokines

  • • Medzhitov R. (2008). Nature. 454(7203):428-35.
  • • Dinarello CA. (2009). Immunol Rev. 227(1):1-11.

TRP & IBD

  • • Julius D. (2013). Nature. 493(7433):551-5.
  • • Khor B, et al. (2011). Nature. 474(7351):307-17.