TNF-alpha is related to the generation of lung fibrosis in patients with UIP. The precise mechanism leading to lung fibrosis by TNF-alpha is unknown. However, the activation of a transcription factor like AP-1(down stream of c-jun N-terminal kinase, JNK) by TNF-alpha may be related to the induction of fibrogenic cytokines like PDGF or IGF-I. Furthermore, JNK was reported to be activated in the radiation-in-duced lung fibrosis model. This study examined JNK activity in patients with UIP.

The expression of phosphorous JNK(p-JNK), macrophage/moncoyte specific markers, CD68, and cytokeratin was evaluated by immunohistochemical (IHC) staining of lung tissues from patients with UIP and lung cancer. An in vitro kinase assay was performed with alveolar macrophages obtained by a bronchollung cancer. An in vitro kinase assay was performed with alvolar macrophages obrtained by a bronchol avleolar lavage from patients with UIP and healthy persons as the control.

The IHC stain showed that p-JNK is expressed in the almost all of the alveolar macrophages and smooth muscle cells in patients with UIP. In case of the normal areas of the lung from patients with lung cancer, the alveolar macrophages showed little p-JNK expression. Interestingly, increased JNK activity was not found in the in vitro kinase assay of the alveolar macrophages obtained from both patients with UIP and healthy persons as the control. Furthermore, 10 ng/ml of TNF-alpha failed to increase the JNK activity of the alveolar macrophages in both patients with UIP and healthy people.

The JNK was activated constitutionally in patients with UIP. However, the role of JNK in the pathogenesis of lung fibrosis needs to be clarified.