TNF-alpha and mucus production in lung epythelium (WP1487)

Rattus norvegicus

The upregulation of mucine is regulated by three different pathways which result in the activation of NF-kB. After TNF-alpha activated its receptor and recruited several adaptor proteins, the IKK complex is activated to inhibit IKBa, resulting in the activation and translocation into the nucleus of NF-kB and upregulation of mucine and IL-6. After EGFR activation by TGF-alpha binding, the RAS-MAPK-pp90 RSK pathway leads to inactivation of IKBa and thus to the translocation of NF-kB. Further, pp90 RSK leads to binding of Sp1 transcription factor to its DNA binding site. By activating Tlr4, LPS can inhibit IKBa.


Julia139 , Kristina Hanspers , Martina Summer-Kutmon , Marianthi Kalafati , and Egon Willighagen


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Rattus norvegicus



Pathway Ontology

signaling pathway


Label Type Compact URI Comment
Ripk2 GeneProduct ncbigene:362491
ERK GeneProduct ncbigene:116590
MEK GeneProduct ncbigene:170851
Tgfa GeneProduct ncbigene:24827
p50 GeneProduct ncbigene:81736
p65 GeneProduct ncbigene:309165
pp90 rsk GeneProduct ncbigene:117269
Sp1 GeneProduct ncbigene:24790
Ras GeneProduct pfam:PF00071
TNFR1 GeneProduct ncbigene:25625
p65 GeneProduct ncbigene:309165
Tnfa GeneProduct ncbigene:24835
Shc GeneProduct ncbigene:85385
Tradd GeneProduct ncbigene:246756
IKKa GeneProduct ncbigene:309361
EGFR GeneProduct ncbigene:24329
Muc5ac GeneProduct ensembl:ENSRNOG00000058420
Traf2 GeneProduct ncbigene:311786
IKKb GeneProduct ncbigene:84351
Raf GeneProduct ncbigene:24703
NF-kB GeneProduct ncbigene:81736
SOS GeneProduct ncbigene:313845
Muc2 GeneProduct ncbigene:24572
p50 GeneProduct ncbigene:81736
IKBa GeneProduct ensembl:ENSRNOG00000007390
Muc5ac GeneProduct ensembl:ENSRNOG00000058420
NF-kB GeneProduct ncbigene:81736
Tlr4 GeneProduct ncbigene:29260
Muc2 GeneProduct ncbigene:24572
Nemo GeneProduct ncbigene:309295
Grb2 GeneProduct ncbigene:81504
Il6 GeneProduct ncbigene:24498


  1. Tumor necrosis factor-alpha triggers mucus production in airway epithelium through an IkappaB kinase beta-dependent mechanism. Lora JM, Zhang DM, Liao SM, Burwell T, King AM, Barker PA, et al. J Biol Chem. 2005 Oct 28;280(43):36510–7. PubMed Europe PMC Scholia