we further conducted experiments to explain the effect of shikonin on NF B signaling pathway. The constitutive activation of NF T signaling is often related to inflammatory and auto-immune conditions. Recently the techniques of regulation or inhibition of NF B signaling is seriously investigated for Oprozomib drug discovery, such as suppression of 26S proteasome and restrict the binding of NF B toDNA. . Inhibition on 26S proteasome has been evident of 1 of the attractive targets for suppressing NF B activation, as it may hinder NF B nuclear translocation, and IB phosphorylation and degradation also. But, the proteasome is involved in the degradation of all polyubiquitinated proteins, thus it’s hard to discover the-most certain inhibitors on the enzymes like E3 ubiquitin ligases and E3 ubiquitin conjugating enzymes,which are accountable for the phosphorylation dependent polyubiquitination of IBs. Considering those difficulties above, searching for the inhibitors on the IKK activity may provide best and selective approach for suppression ofNF Bactivation. Our current data demonstrated that shikonin could PTM considerably suppress NF B signaling pathway through immediate suppression of the IKK activity, revealing reduction of the NF B nuclear translocation, and IB phosphorylation and degradation , IKK phosphorylation.. MAPK cascades play essential role in regulating IL 2 expression, and inhibition of ERK or p38 phosphorylation has been demonstrated to reduce IL 2 expression, which suggests that both of themare needed for T cell activation. Furthermore, JNK could phosphorylate h jun, PFT a part of the AP 1 transcriptional factor family that may generate T-cell activation and is associated with gene transcriptional activity of IL 2. Thus,we investigated the effect of shikonin on MAPK signaling, and the data showed that shikonin inhibited JNK phosphorylation without influence on the phosphorylation of ERK and p38. JNK path appears to perform multiple roles in T cell immune responses, as it can be activated in T cells by stimulation, modulation of cytokine secretion, and cell growth. Taken together, the inhibitory influence of shikonin on human T lymphocytes might mainly result from suppression of IKK activity within the cells. The existing studies have firstly shown immunosuppressive effect of shikonin on human T lymphocytes through suppression of cell activation, while the main molecular mechanisms are associated with inhibition of CD25, CD69 expression, cell routine, NF T and JNK signaling, and IKK exercise. Based on the suppressive influence of shikonin on human T-cells, shikonin could have significant potentials to become investigated as a lead compound for the design and development of the new immunosuppressant for stopping graft rejection and treating auto-immune disorders. Idiopathic pulmonary fibrosis is a chronic lung disorder characterized by fibroblasts growth and extracellular matrix deposition.