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positive regulation of interleukin-1 alpha production

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate, or extent of interleukin-1 alpha production. [GOC:mah]

Positive regulation of interleukin-1 alpha (IL-1α) production is a complex process involving a cascade of molecular events that ultimately lead to the increased synthesis and secretion of this pro-inflammatory cytokine. IL-1α is a key player in the innate immune response, mediating inflammation and promoting the recruitment of immune cells to sites of infection or injury. Its production is tightly regulated to prevent uncontrolled inflammation.

The process of positive regulation of IL-1α production can be summarized as follows:

1. **Signal Recognition and Activation:** The initial step involves the recognition of pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) by pattern recognition receptors (PRRs) expressed on various cell types, including immune cells. These PRRs include Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), and RIG-I-like receptors (RLRs). Upon recognition, PRRs activate downstream signaling pathways.

2. **Signal Transduction and Transcription Factor Activation:** Activated PRRs trigger a series of intracellular signaling events, involving adaptor proteins and kinases. These pathways converge on the activation of transcription factors, such as nuclear factor-κB (NF-κB) and activator protein-1 (AP-1).

3. **IL-1α Gene Transcription:** Activated transcription factors translocate to the nucleus and bind to specific regulatory elements in the IL-1α gene promoter, stimulating its transcription.

4. **IL-1α mRNA Translation and Protein Synthesis:** The transcribed IL-1α mRNA is then translated into the IL-1α protein.

5. **IL-1α Processing and Secretion:** Newly synthesized IL-1α undergoes post-translational modifications, including cleavage by caspase-1, which generates the biologically active form of IL-1α. This processed IL-1α can be secreted from cells via the classical Golgi-dependent pathway or released directly from the cell membrane upon activation of the inflammasome, a multiprotein complex that assembles in response to specific stimuli.

The positive regulation of IL-1α production can be influenced by a variety of factors, including:

* **Inflammatory mediators:** Other pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), can enhance IL-1α production.
* **Pathogen-associated molecules:** Specific components of pathogens, such as lipopolysaccharide (LPS) from bacteria and viral double-stranded RNA, can trigger IL-1α production.
* **Cellular stress signals:** Cellular stress, such as DNA damage or hypoxia, can induce IL-1α expression.
* **Growth factors:** Certain growth factors, such as epidermal growth factor (EGF), can regulate IL-1α production.

Disregulation of IL-1α production can contribute to the development of inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, and sepsis. Therefore, understanding the mechanisms underlying IL-1α production is crucial for developing therapeutic strategies to target these conditions.'
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Proteins (2)

ProteinDefinitionTaxonomy
P2X purinoceptor 7A P2X purinoceptor 7 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q99572]Homo sapiens (human)
Pannexin-1A pannexin-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q96RD7]Homo sapiens (human)

Compounds (20)

CompoundDefinitionClassesRoles
oxatomideoxatomide : A member of the class of benzimidazoles that is 1,3-dihydro-2H-benzimidazol-2-one substituted by a 3-[4-(diphenylmethyl)piperazin-1-yl]propyl group at position 1. It is an anti-allergic drug.

oxatomide: structure; an anti-allergic & an anti-asthmatic
benzimidazoles;
diarylmethane;
N-alkylpiperazine
anti-allergic agent;
anti-inflammatory agent;
geroprotector;
H1-receptor antagonist;
serotonergic antagonist
pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid5'-phosphopyridoxal-6-azobenzene-2,4-disulfonic acid : An arenesulfonic acid that is pyridoxal 5'-phosphate carrying an additional 2,4-disulfophenylazo substituent at position 6.

pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid: a novel antagonist that selectively blocks P2 purinoceptor receptors; a useful tool to study co-transmission in tissues when ATP and coexisting neurotransmitters act in concert
arenesulfonic acid;
azobenzenes;
methylpyridines;
monohydroxypyridine;
organic phosphate;
pyridinecarbaldehyde
purinergic receptor P2X antagonist
probenecidprobenecid : A sulfonamide in which the nitrogen of 4-sulfamoylbenzoic acid is substituted with two propyl groups.

Probenecid: The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy.
benzoic acids;
sulfonamide
uricosuric drug
suraminsuramin : A member of the class of phenylureas that is urea in which each of the amino groups has been substituted by a 3-({2-methyl-5-[(4,6,8-trisulfo-1-naphthyl)carbamoyl]phenyl}carbamoyl)phenyl group. An activator of both the rabbit skeletal muscle RyR1 and sheep cardiac RyR2 isoform ryanodine receptor channels, it has been used for the treatment of human African trypanosomiasis for over 100 years.

Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties.
naphthalenesulfonic acid;
phenylureas;
secondary carboxamide
angiogenesis inhibitor;
antinematodal drug;
antineoplastic agent;
apoptosis inhibitor;
EC 2.7.11.13 (protein kinase C) inhibitor;
GABA antagonist;
GABA-gated chloride channel antagonist;
purinergic receptor P2 antagonist;
ryanodine receptor agonist;
trypanocidal drug
alpha,beta-methyleneadenosine 5'-triphosphatealpha,beta-methyleneadenosine 5'-triphosphate: do not confuse with beta,gamma-methylene ATP; RN given refers to parent cpdnucleoside triphosphate analogue
sb 203580imidazoles;
monofluorobenzenes;
pyridines;
sulfoxide
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor;
geroprotector;
Hsp90 inhibitor;
neuroprotective agent
8-azidoadenosine 5'-triphosphate
6-thioinosine-5'-triphosphateorganic molecule
mrs2159MRS2159: an antagonist of both P2X1 and P2X7 receptors
imd 0354N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide: a cardioprotective agent that inhibits IkappaB kinase beta (IKKbeta); structure in first sourcebenzamides
kn 62KN 62: inhibitor of Ca/calmodulin-dependent protein kinase IIpiperazines
az 11645373AZ 11645373: InChIKey: VQEHBLGYANQWEA-UHFFFAOYSA-N
az10606120AZ10606120: a P2X7 receptor antagonist
ce 224,535CE 224,535: structure in first source
a-438079
af 3535-(5-iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine: a P2X3 and P2X2/3 receptor antagonist; structure in first source
gsk1482160
a-839977A-839977: a selective P2X7 receptor antagonist, analgesic; structure in first source
jnj-47965567JNJ-47965567: a P2X7 purinergic receptor antagonist; structure in first source
mk-8742elbasvir : A complex organic heterotetracyclic compound that is a hepatitis C virus nonstructural protein 5A inhibitor used in combination with grazoprevir (under the brand name Zepatier) for treatment of chronic HCV genotypes 1 or 4 infection in adults.

elbasvir: inhibits NS5A protein of hepatitis C virus
carbamate ester;
imidazoles;
L-valine derivative;
N-acylpyrrolidine;
organic heterotetracyclic compound;
ring assembly
antiviral drug;
hepatitis C virus nonstructural protein 5A inhibitor;
hepatoprotective agent